ClinVar Genomic variation as it relates to human health
NM_000249.4(MLH1):c.825del (p.Ala275_Ile276insTer)
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_000249.4(MLH1):c.825del (p.Ala275_Ile276insTer)
Variation ID: 2120140 Accession: VCV002120140.2
- Type and length
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Deletion, 1 bp
- Location
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Cytogenetic: 3p22.2 3: 37017539 (GRCh38) [ NCBI UCSC ] 3: 37059030 (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 Feb 8, 2023 Feb 20, 2024 Apr 1, 2022 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000249.4:c.825del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000240.1:p.Ala275_Ile276insTer frameshift NM_001167617.3:c.531del NP_001161089.1:p.Ala177_Ile178insTer frameshift NM_001167618.3:c.102del NP_001161090.1:p.Ala34_Ile35insTer frameshift NM_001167619.3:c.102del NP_001161091.1:p.Ala34_Ile35insTer frameshift NM_001258271.2:c.825del NP_001245200.1:p.Ala275_Ile276insTer frameshift NM_001258273.2:c.102del NP_001245202.1:p.Ala34_Ile35insTer frameshift NM_001258274.3:c.102del NP_001245203.1:p.Ala34_Ile35insTer frameshift NM_001354615.2:c.102del NP_001341544.1:p.Ala34_Ile35insTer frameshift NM_001354616.2:c.102del NP_001341545.1:p.Ala34_Ile35insTer frameshift NM_001354617.2:c.102del NP_001341546.1:p.Ala34_Ile35insTer frameshift NM_001354618.2:c.102del NP_001341547.1:p.Ala34_Ile35insTer frameshift NM_001354619.2:c.102del NP_001341548.1:p.Ala34_Ile35insTer frameshift NM_001354620.2:c.531del NP_001341549.1:p.Ala177_Ile178insTer frameshift NM_001354621.2:c.-139-2770del intron variant NM_001354622.2:c.-139-2770del intron variant NM_001354623.2:c.-139-2770del intron variant NM_001354624.2:c.-37+2996del intron variant NM_001354625.2:c.-37+2996del intron variant NM_001354626.2:c.-37+2996del intron variant NM_001354627.2:c.-37+2996del intron variant NM_001354628.2:c.825del NP_001341557.1:p.Ala275_Ile276insTer frameshift NM_001354629.2:c.726del NP_001341558.1:p.Ala242_Ile243insTer frameshift NM_001354630.2:c.825del NP_001341559.1:p.Ala275_Ile276insTer frameshift NC_000003.12:g.37017540del NC_000003.11:g.37059031del NG_007109.2:g.29191del LRG_216:g.29191del LRG_216t1:c.825del LRG_216p1:p.Ile276Terfs - Protein change
- Other names
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- Canonical SPDI
- NC_000003.12:37017538:CC: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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Allele frequency
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The frequency of the allele represented by this VCV record.
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- Links
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
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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
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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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MLH1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
5529 | 5584 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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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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Pathogenic (1) |
criteria provided, single submitter
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Apr 1, 2022 | RCV003025002.2 |
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
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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
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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
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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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Pathogenic
(Apr 01, 2022)
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criteria provided, single submitter
Method: clinical testing
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Hereditary nonpolyposis colorectal neoplasms
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV003334932.2
First in ClinVar: Feb 07, 2023 Last updated: Feb 20, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with MLH1-related conditions. … (more)
For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with MLH1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ile276*) in the MLH1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MLH1 are known to be pathogenic (PMID: 15713769, 24362816). (less)
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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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Application of a 5-tiered scheme for standardized classification of 2,360 unique mismatch repair gene variants in the InSiGHT locus-specific database. | Thompson BA | Nature genetics | 2014 | PMID: 24362816 |
Conversion analysis for mutation detection in MLH1 and MSH2 in patients with colorectal cancer. | Casey G | JAMA | 2005 | PMID: 15713769 |
Text-mined citations for this variant ...
HelpRecord last updated Feb 20, 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.