ClinVar Genomic variation as it relates to human health
NM_000249.4(MLH1):c.2011del (p.Glu671fs)
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.2011del (p.Glu671fs)
Variation ID: 2447082 Accession: VCV002447082.1
- Type and length
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Deletion, 1 bp
- Location
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Cytogenetic: 3p22.2 3: 37048924 (GRCh38) [ NCBI UCSC ] 3: 37090415 (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 15, 2023 Apr 15, 2023 Nov 10, 2022 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000249.4:c.2011del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000240.1:p.Glu671fs frameshift NM_001167617.3:c.1717del NP_001161089.1:p.Glu573fs frameshift NM_001167618.3:c.1288del NP_001161090.1:p.Glu430fs frameshift NM_001167619.3:c.1288del NP_001161091.1:p.Glu430fs frameshift NM_001258271.2:c.1896+1242del intron variant NM_001258273.2:c.1288del NP_001245202.1:p.Glu430fs frameshift NM_001258274.3:c.1288del NP_001245203.1:p.Glu430fs frameshift NM_001354615.2:c.1288del NP_001341544.1:p.Glu430fs frameshift NM_001354616.2:c.1288del NP_001341545.1:p.Glu430fs frameshift NM_001354617.2:c.1288del NP_001341546.1:p.Glu430fs frameshift NM_001354618.2:c.1288del NP_001341547.1:p.Glu430fs frameshift NM_001354619.2:c.1288del NP_001341548.1:p.Glu430fs frameshift NM_001354620.2:c.1717del NP_001341549.1:p.Glu573fs frameshift NM_001354621.2:c.988del NP_001341550.1:p.Glu330fs frameshift NM_001354622.2:c.988del NP_001341551.1:p.Glu330fs frameshift NM_001354623.2:c.988del NP_001341552.1:p.Glu330fs frameshift NM_001354624.2:c.937del NP_001341553.1:p.Glu313fs frameshift NM_001354625.2:c.937del NP_001341554.1:p.Glu313fs frameshift NM_001354626.2:c.937del NP_001341555.1:p.Glu313fs frameshift NM_001354627.2:c.937del NP_001341556.1:p.Glu313fs frameshift NM_001354628.2:c.1918del NP_001341557.1:p.Glu640fs frameshift NM_001354629.2:c.1912del NP_001341558.1:p.Glu638fs frameshift NM_001354630.2:c.1846del NP_001341559.1:p.Glu616fs frameshift NC_000003.12:g.37048925del NC_000003.11:g.37090416del NG_007109.2:g.60576del LRG_216:g.60576del LRG_216t1:c.2011del LRG_216p1:p.Glu671Asnfs - Protein change
- E638fs, E640fs, E313fs, E330fs, E430fs, E671fs, E573fs, E616fs
- Other names
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- Canonical SPDI
- NC_000003.12:37048923:GG:G
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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
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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
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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 |
5531 | 5586 |
Conditions - Germline
Condition
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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
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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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Nov 10, 2022 | RCV003176303.1 |
Submissions - Germline
Classification
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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
(Nov 10, 2022)
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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: SCV003861020.1
First in ClinVar: Apr 15, 2023 Last updated: Apr 15, 2023 |
Comment:
The c.2011delG variant, located in coding exon 18 of the MLH1 gene, results from a deletion of one nucleotide at nucleotide position 2011, causing a … (more)
The c.2011delG variant, located in coding exon 18 of the MLH1 gene, results from a deletion of one nucleotide at nucleotide position 2011, causing a translational frameshift with a predicted alternate stop codon (p.E671Nfs*112). This alteration occurs at the 3' terminus of the MLH1gene, is not expected to trigger nonsense-mediated mRNAdecay and results in the elongation of the protein by 26 amino acids. This frameshift impacts the last 11% amino acids of the native protein. However, frameshifts are typically deleterious in nature and the impacted region is critical for protein function (Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). As such, this alteration is interpreted as a disease-causing mutation. (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
HelpThere are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar. |
Text-mined citations for this variant ...
HelpRecord last updated Dec 25, 2023
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.