ClinVar Genomic variation as it relates to human health
NM_000249.4(MLH1):c.1517T>C (p.Val506Ala)
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.
Pathogenic(1); Likely pathogenic(9); Uncertain significance(1)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000249.4(MLH1):c.1517T>C (p.Val506Ala)
Variation ID: 89757 Accession: VCV000089757.39
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 3p22.2 3: 37028891 (GRCh38) [ NCBI UCSC ] 3: 37070382 (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 Mar 24, 2015 Jun 17, 2024 Feb 20, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000249.4:c.1517T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000240.1:p.Val506Ala missense NM_001167617.3:c.1223T>C NP_001161089.1:p.Val408Ala missense NM_001167618.3:c.794T>C NP_001161090.1:p.Val265Ala missense NM_001167619.3:c.794T>C NP_001161091.1:p.Val265Ala missense NM_001258271.2:c.1517T>C NP_001245200.1:p.Val506Ala missense NM_001258273.2:c.794T>C NP_001245202.1:p.Val265Ala missense NM_001258274.3:c.794T>C NP_001245203.1:p.Val265Ala missense NM_001354615.2:c.794T>C NP_001341544.1:p.Val265Ala missense NM_001354616.2:c.794T>C NP_001341545.1:p.Val265Ala missense NM_001354617.2:c.794T>C NP_001341546.1:p.Val265Ala missense NM_001354618.2:c.794T>C NP_001341547.1:p.Val265Ala missense NM_001354619.2:c.794T>C NP_001341548.1:p.Val265Ala missense NM_001354620.2:c.1223T>C NP_001341549.1:p.Val408Ala missense NM_001354621.2:c.494T>C NP_001341550.1:p.Val165Ala missense NM_001354622.2:c.494T>C NP_001341551.1:p.Val165Ala missense NM_001354623.2:c.494T>C NP_001341552.1:p.Val165Ala missense NM_001354624.2:c.443T>C NP_001341553.1:p.Val148Ala missense NM_001354625.2:c.443T>C NP_001341554.1:p.Val148Ala missense NM_001354626.2:c.443T>C NP_001341555.1:p.Val148Ala missense NM_001354627.2:c.443T>C NP_001341556.1:p.Val148Ala missense NM_001354628.2:c.1517T>C NP_001341557.1:p.Val506Ala missense NM_001354629.2:c.1418T>C NP_001341558.1:p.Val473Ala missense NM_001354630.2:c.1517T>C NP_001341559.1:p.Val506Ala missense NC_000003.12:g.37028891T>C NC_000003.11:g.37070382T>C NG_007109.2:g.40542T>C LRG_216:g.40542T>C LRG_216t1:c.1517T>C LRG_216p1:p.Val506Ala P40692:p.Val506Ala - Protein change
- V506A, V408A, V473A, V148A, V165A, V265A
- Other names
- p.V506A:GTT>GCT
- Canonical SPDI
- NC_000003.12:37028890:T: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
Help
The frequency of the allele represented by this VCV record.
Trans-Omics for Precision Medicine (TOPMed) 0.00000
The Genome Aggregation Database (gnomAD) 0.00001
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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MLH1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
5632 | 5687 |
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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Likely pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Apr 26, 2023 | RCV000160534.24 | |
Conflicting interpretations of pathogenicity (4) |
criteria provided, conflicting classifications
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Sep 5, 2023 | RCV000174455.23 | |
Likely pathogenic (1) |
criteria provided, single submitter
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Jun 6, 2019 | RCV000259153.19 | |
Pathogenic (1) |
criteria provided, single submitter
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Jan 27, 2024 | RCV000524242.15 | |
Likely pathogenic (1) |
criteria provided, single submitter
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Mar 27, 2023 | RCV001778701.10 | |
MLH1-related disorder
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Likely pathogenic (1) |
criteria provided, single submitter
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Mar 1, 2023 | RCV003398662.4 |
Likely pathogenic (1) |
criteria provided, single submitter
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Feb 20, 2024 | RCV003466955.2 |
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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Likely pathogenic
(Mar 27, 2023)
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criteria provided, single submitter
Method: clinical testing
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Hereditary nonpolyposis colon cancer
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000919651.3
First in ClinVar: Jun 03, 2019 Last updated: May 13, 2023 |
Comment:
Variant summary: MLH1 c.1517T>C (p.Val506Ala) results in a non-conservative amino acid change located in the C-terminal domain (IPR032189) of the encoded protein sequence. Five of … (more)
Variant summary: MLH1 c.1517T>C (p.Val506Ala) results in a non-conservative amino acid change located in the C-terminal domain (IPR032189) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 3.8e-06 in 261636 control chromosomes (gnomAD). c.1517T>C has been reported in multiple colorectal cancer patients from families fulfilling the Amsterdam and the revised Bethesda criteria (e.g. Liu_1996, Chao_2008, Yurgelun_2015, Syngal_1999, Medeiros_2012). These data indicate that the variant is likely to be associated with disease. In in vitro functional studies, the variant showed reduced MLH1 expression and altered binding to PMS2 and EXO1, but mismatch repair (MMR) activity close to wild type (Shimodaira_1998, Guerrette_1999, Takahashi_2007, Hinrichsen_2013). Eight (other) submitters have provided clinical-significance assessments for this variant to ClinVar after 2014, and classified it as pathogenic/likely pathogenic (n=7) or uncertain significance (n=1). Based on the evidence outlined above, the variant was classified as likely pathogenic. (less)
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Likely pathogenic
(Sep 05, 2023)
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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: SCV000211106.15
First in ClinVar: Feb 24, 2015 Last updated: Sep 30, 2023 |
Comment:
Observed in multiple individuals with personal and family history consistent with Lynch syndrome (Liu et al., 1996; Syngal et al., 1999; Chao et al., 2008); … (more)
Observed in multiple individuals with personal and family history consistent with Lynch syndrome (Liu et al., 1996; Syngal et al., 1999; Chao et al., 2008); Published functional studies demonstrate a damaging effect with respect to a dominant mutator effect, MLH1 expression, and PMS2 and EXO1 binding, while studies assessing mismatch repair activity show results comparable to wild-type (Shimodaira et al., 1998; Guerrette et al., 1999; Kondo et al., 2003; Takahashi et al., 2007; Hinrichsen et al., 2013); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 8574961, 17594722, 10037723, 22949387, 10422993, 12810663, 19015241, 25980754, 17192056, 10874307, 18383312, 22290698, 19690142, 22788692, 22658618, 22426235, 19250818, 11292842, 31697235, 31391288, 32719484, 32427313, 30787465, 17510385, 23403630, 9697702, 36054288, 31784484, 12799449, 20533529, 22753075) (less)
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Likely pathogenic
(Apr 22, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
unknown
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Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000601359.3
First in ClinVar: Dec 06, 2016 Last updated: Jan 06, 2024 |
Comment:
The frequency of this variant in the general population, 0.000032 (1/31390 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. In the published literature, the … (more)
The frequency of this variant in the general population, 0.000032 (1/31390 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. In the published literature, the variant has been reported in individuals with Lynch syndrome (PMID: 8574961 (1996), 19690142 (2009), 22949387 (2013), 23403630 (2013), 25980754 (2015)). Multiple studies have reported on the functional effect of this variant, some indicating a detrimental effect and others indicating no detrimental effect of the variant on protein function. It has been identified in tumors with high microsatellite instability, as well as associated with reduced interaction with PMS2 and decreased/defective mismatch repair activity (PMID: 9697702 (1998), PMID: 10037723 (1999), and PMID: 22949387 (2013)). In contrast, it has been claimed to be repair-proficient despite observed reduced stability and expression of MLH1 (PMID: 23403630 (2013)). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is damaging. Based on the available information, this variant is classified as likely pathogenic. (less)
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Likely pathogenic
(Aug 04, 2022)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Revvity Omics, Revvity
Accession: SCV003830995.2
First in ClinVar: Mar 04, 2023 Last updated: Feb 04, 2024 |
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Likely pathogenic
(Apr 11, 2023)
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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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Color Diagnostics, LLC DBA Color Health
Accession: SCV000911974.4
First in ClinVar: May 20, 2019 Last updated: Feb 14, 2024 |
Comment:
This missense variant replaces valine with alanine at codon 506 of the MLH1 protein. Computational prediction suggests that this variant may have deleterious impact on … (more)
This missense variant replaces valine with alanine at codon 506 of the MLH1 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). Functional studies have shown that this variant reduced MLH1 protein expression (PMID: 9697702, 17510385, 23403630), disrupted PMS2 and EXO1 binding activity (PMID: 10037723, 12810663), and reduced dominant mutator effect (PMID: 9697702, 17510385). However, the impact of this variant on DNA mismatch repair activity remains unclear (PMID: 17510385, 23403630, 36054288). This variant has been reported in individuals and families affected with Lynch Syndrome (PMID: 8574961, 18383312, 19250818, 22426235, 25980754, 31391288). This variant has been identified in 1/31390 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Likely Pathogenic. (less)
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Likely pathogenic
(Apr 26, 2023)
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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: SCV000212722.8
First in ClinVar: Mar 24, 2015 Last updated: May 01, 2024 |
Comment:
The p.V506A variant (also known as c.1517T>C), located in coding exon 13 of the MLH1 gene, results from a T to C substitution at nucleotide … (more)
The p.V506A variant (also known as c.1517T>C), located in coding exon 13 of the MLH1 gene, results from a T to C substitution at nucleotide position 1517. The valine at codon 506 is replaced by alanine, an amino acid with similar properties. This alteration was identified in several individuals whose family history met Amsterdam I/II criteria for Lynch syndrome and/or tumors showed loss of MLH1 and/or PMS2 protein expression on immunohistochemistry (IHC) as well as high microsatellite instability (MSI-H) (Ambry internal data; Liu B et al. Nat. Med. 1996 Feb;2:169-74; ). This alteration has also been observed in an individual whose colorectal tumor demonstrated normal mismatch repair protein expression on IHC (Ambry internal data). Multiple yeast-based functional studies of this variant have demonstrated reduced binding of the V506A hMLH1 protein with hPMS2 when compared to wild-type hMLH1 (Guerrette S et al. J. Biol. Chem. 1999 Mar 5;274:6336-41; Kondo E et al. Cancer Res. 2003 Jun;63:3302-8; Shimodaira H et al. Nat. Genet. 1998 Aug;19:384-9). Further, multiple functional studies where cell lines were transfected with this alteration have been shown to exhibit reduced MLH1 expression; however, in vitro functional assays showed that mismatch repair activity was comparable to wild-type (Hinrichsen I et al. Clin. Cancer Res. 2013 May;19:2432-41; Takahashi M et al. Cancer Res. 2007 May;67:4595-604). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic. (less)
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Likely pathogenic
(Feb 20, 2024)
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criteria provided, single submitter
Method: clinical testing
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Colorectal cancer, hereditary nonpolyposis, type 2
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004190618.2
First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024 |
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Uncertain significance
(Sep 15, 2017)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Eurofins Ntd Llc (ga)
Accession: SCV000225761.5
First in ClinVar: Jun 29, 2015 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 1
Sex: mixed
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Likely pathogenic
(Jun 06, 2019)
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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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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000885704.2
First in ClinVar: Dec 15, 2018 Last updated: Feb 09, 2020 |
Comment:
The MLH1 c.1517T>C; p.Val506Ala variant has been described in individuals and families that met diagnostic criteria for Lynch syndrome (Chao 2008, Liu 1996, Syngal 1999), … (more)
The MLH1 c.1517T>C; p.Val506Ala variant has been described in individuals and families that met diagnostic criteria for Lynch syndrome (Chao 2008, Liu 1996, Syngal 1999), and segregates with disease in several unrelated families (internal data, personal communication with GeneDx and Invitae). In vitro functional analyses demonstrate reduced protein expression, but close to wild-type mismatch repair activity (Hinrichsen 2013, Takahashi 2007). Additionally, yeast two hybrid assays have demonstrated reduced functional outputs (Kondo 2003, Shimodaira 1998). This variant is reported in ClinVar (Variation ID: 89757), and is only observed on one allele in the Genome Aggregation Database, indicating it is not a common polymorphism. The valine at codon 506 is moderately conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. Based on available information, this variant is considered to be likely pathogenic. References: Chao EC et al. Accurate classification of MLH1/MSH2 missense variants with multivariate analysis of protein polymorphisms-mismatch repair (MAPP-MMR). Hum Mutat. 2008 Jun;29(6):852-60. Hinrichsen I et al. Expression defect size among unclassified MLH1 variants determines pathogenicity in Lynch syndrome diagnosis. Clin Cancer Res. 2013 May 1;19(9):2432-41. Kondo E et al. A yeast two-hybrid assay provides a simple way to evaluate the vast majority of hMLH1 germ-line mutations. Cancer Res. 2003 Jun 15;63(12):3302-8. Liu B et al. Analysis of mismatch repair genes in hereditary non-polyposis colorectal cancer patients. Nat Med. 1996 Feb;2(2):169-74. Shimodaira H et al. Functional analysis of human MLH1 mutations in Saccharomyces cerevisiae. Nat Genet. 1998 Aug;19(4):384-9. Syngal S et al. Interpretation of genetic test results for hereditary nonpolyposis colorectal cancer: implications for clinical predisposition testing. JAMA. 1999 Jul 21;282(3):247-53. Takahashi M et al. Functional analysis of human MLH1 variants using yeast and in vitro mismatch repair assays. Cancer Res. 2007 May 15;67(10):4595-604. (less)
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Likely pathogenic
(Mar 01, 2023)
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criteria provided, single submitter
Method: clinical testing
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MLH1-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV004111858.1
First in ClinVar: Nov 20, 2023 Last updated: Nov 20, 2023 |
Comment:
The MLH1 c.1517T>C variant is predicted to result in the amino acid substitution p.Val506Ala. This variant has been reported in families with hereditary non-polyposis colorectal … (more)
The MLH1 c.1517T>C variant is predicted to result in the amino acid substitution p.Val506Ala. This variant has been reported in families with hereditary non-polyposis colorectal cancer (Table 2, Liu et al. 1996. PubMed ID: 8574961; Table 3, Syngal et al. 1999. PubMed ID: 10422993; Table S1, Chao et al. 2008. PubMed ID: 18383312). It has been reported in individuals undergoing Lynch syndrome population screening, as well as an unaffected individual from a breast cancer cohort study (Table S3, Grzymski et al. 2020. PubMed ID: 32719484; Table S3, Palmer et al. 2020. PubMed ID: 32427313). In vitro experimental studies suggest this variant leads to reduced binding to hPMS2, reduced MMR activity, and reduced protein expression (Guerrette et al. 1999. PubMed ID: 10037723; Figure 1, Hinrichsen et al. 2013. PubMed ID: 23403630; Table S1, Ou et al. 2007. PubMed ID: 17594722; Table 1, Takahashi et al. 2007. PubMed ID: 17510385). In vivo experimental studies suggest this variant reduces binding to EXO1 and inactivates the dominant negative phenotype of hMLH1 in some strains of yeast (Table 1, Figure 3b, Shimodaira et al. 1998. PubMed ID: 9697702; Table 1, Kondo et al 2003. PubMed ID: 12810663; Table 1, Takahashi et al. 2007. PubMed ID: 17510385). This variant is reported in 1 of ~31,000 alleles in gnomAD (http://gnomad.broadinstitute.org/variant/3-37070382-T-C). It is interpreted as likely pathogenic by the vast majority of submitters in ClinVar (https://preview.ncbi.nlm.nih.gov/clinvar/variation/89757/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. (less)
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Pathogenic
(Jan 27, 2024)
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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: SCV000543586.8
First in ClinVar: Mar 24, 2015 Last updated: Feb 28, 2024 |
Comment:
This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 506 of the MLH1 protein (p.Val506Ala). … (more)
This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 506 of the MLH1 protein (p.Val506Ala). This variant is present in population databases (rs63749909, gnomAD 0.007%). This missense change has been observed in individuals with Lynch syndrome (PMID: 8574961, 10422993, 18383312; Invitae). ClinVar contains an entry for this variant (Variation ID: 89757). An algorithm developed specifically for the MLH1 gene suggests that this missense change is likely to be deleterious (PMID: 18383312). Experimental studies have shown that this missense change affects MLH1 function (PMID: 9697702, 10037723, 12810663, 17510385, 23403630). For these reasons, this variant has been classified as Pathogenic. (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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A calibrated cell-based functional assay to aid classification of MLH1 DNA mismatch repair gene variants. | Rath A | Human mutation | 2022 | PMID: 36054288 |
Physician-directed genetic screening to evaluate personal risk for medically actionable disorders: a large multi-center cohort study. | Haverfield EV | BMC medicine | 2021 | PMID: 34404389 |
Population genetic screening efficiently identifies carriers of autosomal dominant diseases. | Grzymski JJ | Nature medicine | 2020 | PMID: 32719484 |
Contribution of Germline Predisposition Gene Mutations to Breast Cancer Risk in African American Women. | Palmer JR | Journal of the National Cancer Institute | 2020 | PMID: 32427313 |
Three-step site-directed mutagenesis screen identifies pathogenic MLH1 variants associated with Lynch syndrome. | Houlleberghs H | Journal of medical genetics | 2020 | PMID: 31784484 |
Tumour characteristics provide evidence for germline mismatch repair missense variant pathogenicity. | Li S | Journal of medical genetics | 2020 | PMID: 31391288 |
Computational and cellular studies reveal structural destabilization and degradation of MLH1 variants in Lynch syndrome. | Abildgaard AB | eLife | 2019 | PMID: 31697235 |
Multigene Panel Testing Provides a New Perspective on Lynch Syndrome. | Espenschied CR | Journal of clinical oncology : official journal of the American Society of Clinical Oncology | 2017 | PMID: 28514183 |
Identification of a Variety of Mutations in Cancer Predisposition Genes in Patients With Suspected Lynch Syndrome. | Yurgelun MB | Gastroenterology | 2015 | PMID: 25980754 |
Expression defect size among unclassified MLH1 variants determines pathogenicity in Lynch syndrome diagnosis. | Hinrichsen I | Clinical cancer research : an official journal of the American Association for Cancer Research | 2013 | PMID: 23403630 |
Calibration of multiple in silico tools for predicting pathogenicity of mismatch repair gene missense substitutions. | Thompson BA | Human mutation | 2013 | PMID: 22949387 |
Colon cancer associated genes exhibit signatures of positive selection at functionally significant positions. | Morgan CC | BMC evolutionary biology | 2012 | PMID: 22788692 |
ColoSeq provides comprehensive lynch and polyposis syndrome mutational analysis using massively parallel sequencing. | Pritchard CC | The Journal of molecular diagnostics : JMD | 2012 | PMID: 22658618 |
The germline MLH1 K618A variant and susceptibility to Lynch syndrome-associated tumors. | Medeiros F | The Journal of molecular diagnostics : JMD | 2012 | PMID: 22426235 |
Comprehensive molecular analysis of mismatch repair gene defects in suspected Lynch syndrome (hereditary nonpolyposis colorectal cancer) cases. | Mueller J | Cancer research | 2009 | PMID: 19690142 |
A new strategy to screen MMR genes in Lynch Syndrome: HA-CAE, MLPA and RT-PCR. | Perez-Cabornero L | European journal of cancer (Oxford, England : 1990) | 2009 | PMID: 19250818 |
Characterization of a highly conserved binding site of Mlh1 required for exonuclease I-dependent mismatch repair. | Dherin C | Molecular and cellular biology | 2009 | PMID: 19015241 |
Accurate classification of MLH1/MSH2 missense variants with multivariate analysis of protein polymorphisms-mismatch repair (MAPP-MMR). | Chao EC | Human mutation | 2008 | PMID: 18383312 |
Functional analysis helps to clarify the clinical importance of unclassified variants in DNA mismatch repair genes. | Ou J | Human mutation | 2007 | PMID: 17594722 |
Functional analysis of human MLH1 variants using yeast and in vitro mismatch repair assays. | Takahashi M | Cancer research | 2007 | PMID: 17510385 |
The use of microsatellite instability, immunohistochemistry and other variables in determining the clinical significance of MLH1 and MSH2 unclassified variants in Lynch syndrome. | Lucci-Cordisco E | Cancer biomarkers : section A of Disease markers | 2006 | PMID: 17192056 |
A yeast two-hybrid assay provides a simple way to evaluate the vast majority of hMLH1 germ-line mutations. | Kondo E | Cancer research | 2003 | PMID: 12810663 |
The interacting domains of three MutL heterodimers in man: hMLH1 interacts with 36 homologous amino acid residues within hMLH3, hPMS1 and hPMS2. | Kondo E | Nucleic acids research | 2001 | PMID: 11292842 |
Interpretation of genetic test results for hereditary nonpolyposis colorectal cancer: implications for clinical predisposition testing. | Syngal S | JAMA | 1999 | PMID: 10422993 |
The interaction of the human MutL homologues in hereditary nonpolyposis colon cancer. | Guerrette S | The Journal of biological chemistry | 1999 | PMID: 10037723 |
Functional analysis of human MLH1 mutations in Saccharomyces cerevisiae. | Shimodaira H | Nature genetics | 1998 | PMID: 9697702 |
Analysis of mismatch repair genes in hereditary non-polyposis colorectal cancer patients. | Liu B | Nature medicine | 1996 | PMID: 8574961 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=MLH1 | - | - | - | - |
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Text-mined citations for rs63749909 ...
HelpRecord last updated Jun 17, 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.