ClinVar Genomic variation as it relates to human health
NM_000222.3(KIT):c.1621A>C (p.Met541Leu)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000222.3(KIT):c.1621A>C (p.Met541Leu)
Variation ID: 41599 Accession: VCV000041599.23
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 4q12 4: 54727298 (GRCh38) [ NCBI UCSC ] 4: 55593464 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Apr 12, 2013 Feb 14, 2024 Feb 1, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000222.3:c.1621A>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000213.1:p.Met541Leu missense NM_001093772.2:c.1609A>C NP_001087241.1:p.Met537Leu missense NM_001385284.1:c.1624A>C NP_001372213.1:p.Met542Leu missense NM_001385285.1:c.1621A>C NP_001372214.1:p.Met541Leu missense NM_001385286.1:c.1609A>C NP_001372215.1:p.Met537Leu missense NM_001385288.1:c.1612A>C NP_001372217.1:p.Met538Leu missense NM_001385290.1:c.1624A>C NP_001372219.1:p.Met542Leu missense NM_001385292.1:c.1612A>C NP_001372221.1:p.Met538Leu missense NC_000004.12:g.54727298A>C NC_000004.11:g.55593464A>C NG_007456.1:g.74304A>C LRG_307:g.74304A>C LRG_307t1:c.1621A>C LRG_307p1:p.Met541Leu P10721:p.Met541Leu - Protein change
- M541L, M537L, M538L, M542L
- Other names
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- Canonical SPDI
- NC_000004.12:54727297:A:C
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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0.06450 (C)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
1000 Genomes Project 0.06450
1000 Genomes Project 30x 0.06465
The Genome Aggregation Database (gnomAD) 0.07727
Exome Aggregation Consortium (ExAC) 0.07889
Trans-Omics for Precision Medicine (TOPMed) 0.07942
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.09549
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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KIT | - | - |
GRCh38 GRCh37 |
2794 | 2820 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Benign (2) |
criteria provided, single submitter
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Jun 22, 2018 | RCV000034504.5 | |
Benign (4) |
criteria provided, single submitter
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- | RCV000121313.9 | |
Likely benign (1) |
criteria provided, single submitter
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Apr 27, 2017 | RCV000261290.6 | |
Likely benign (1) |
criteria provided, single submitter
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Apr 27, 2017 | RCV000315844.6 | |
Benign/Likely benign (3) |
criteria provided, multiple submitters, no conflicts
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Feb 1, 2024 | RCV000370023.13 | |
not provided (1) |
no classification provided
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Mar 10, 2016 | RCV000422326.2 | |
Benign (1) |
criteria provided, single submitter
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May 8, 2019 | RCV001012439.3 | |
Pathogenic (1) |
no assertion criteria provided
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Apr 30, 2019 | RCV001255636.2 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Benign
(-)
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criteria provided, single submitter
Method: clinical testing
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NOT SPECIFIED
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV000303052.1
First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016 |
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Benign
(May 08, 2019)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV001172890.3
First in ClinVar: Mar 16, 2020 Last updated: Nov 29, 2022 |
Comment:
This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA … (more)
This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
Number of individuals with the variant: 1
|
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Benign
(Jul 07, 2023)
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criteria provided, single submitter
Method: clinical testing
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Gastrointestinal stromal tumor
Affected status: yes
Allele origin:
germline
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KCCC/NGS Laboratory, Kuwait Cancer Control Center
Accession: SCV004015783.1
First in ClinVar: Jul 29, 2023 Last updated: Jul 29, 2023 |
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Likely benign
(Apr 27, 2017)
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criteria provided, single submitter
Method: clinical testing
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Piebaldism
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000449888.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less)
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Likely benign
(Apr 27, 2017)
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criteria provided, single submitter
Method: clinical testing
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Gastrointestinal stromal tumor
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000449886.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less)
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Likely benign
(Apr 27, 2017)
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criteria provided, single submitter
Method: clinical testing
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Cutaneous mastocytosis
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000449887.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less)
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Benign
(Jun 22, 2018)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV001882956.1
First in ClinVar: Sep 19, 2021 Last updated: Sep 19, 2021 |
Comment:
This variant is associated with the following publications: (PMID: 27153395, 18795925, 24728327, 22703879)
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Benign
(Feb 01, 2024)
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criteria provided, single submitter
Method: clinical testing
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Gastrointestinal stromal tumor
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV001716496.4
First in ClinVar: Jun 15, 2021 Last updated: Feb 14, 2024 |
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no known pathogenicity
(Jul 13, 2012)
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no assertion criteria provided
Method: research
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not provided
Affected status: no
Allele origin:
germline
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Biesecker Lab/Clinical Genomics Section, National Institutes of Health
Study: ClinSeq
Accession: SCV000043281.1 First in ClinVar: Apr 12, 2013 Last updated: Apr 12, 2013 |
Comment:
Converted during submission to Benign.
Number of individuals with the variant: 113
Comment on evidence:
The study set was not selected for affection status in relation to any cancer. Pathogenicity categories were based on literature curation. See Pubmed ID:22703879 for … (more)
The study set was not selected for affection status in relation to any cancer. Pathogenicity categories were based on literature curation. See Pubmed ID:22703879 for details. (less)
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Pathogenic
(Apr 30, 2019)
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no assertion criteria provided
Method: research
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Lip and oral cavity carcinoma
Affected status: yes
Allele origin:
somatic
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Institute of Medical Sciences, Banaras Hindu University
Accession: SCV001432197.1
First in ClinVar: Sep 14, 2020 Last updated: Sep 14, 2020 |
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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Genome Diagnostics Laboratory, University Medical Center Utrecht
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001977832.1 First in ClinVar: Oct 16, 2021 Last updated: Oct 16, 2021 |
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001979651.1 First in ClinVar: Oct 16, 2021 Last updated: Oct 16, 2021 |
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not provided
(Sep 19, 2013)
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no classification provided
Method: reference population
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AllHighlyPenetrant
Affected status: unknown
Allele origin:
germline
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ITMI
Accession: SCV000085484.1
First in ClinVar: Jun 09, 2014 Last updated: Jun 09, 2014 |
Observation 1:
Ethnicity/Population group: Whole_cohort
Observation 2:
Ethnicity/Population group: African
Observation 3:
Ethnicity/Population group: African_European
Observation 4:
Ethnicity/Population group: Central_Asian
Observation 5:
Ethnicity/Population group: East_Asian
Observation 6:
Ethnicity/Population group: European
Observation 7:
Ethnicity/Population group: Hispanic
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not provided
(Mar 10, 2016)
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no classification provided
Method: literature only
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Chronic myelogenous leukemia, BCR-ABL1 positive
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
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Database of Curated Mutations (DoCM)
Accession: SCV000505727.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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The c-kit (CD117) sequence variation M541L, but not N564K, is frequent in the general population, and is not associated with CML in Caucasians. | Krüger S | Leukemia | 2006 | PMID: 16307017 |
http://docm.genome.wustl.edu/variants/ENST00000288135:c.1621A>C | - | - | - | - |
Text-mined citations for rs3822214 ...
HelpRecord last updated Apr 15, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.