ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.1462T>G (p.Leu488Val)

gnomAD frequency: 0.00001  dbSNP: rs587781314
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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129044 SCV000172956 likely benign Hereditary cancer-predisposing syndrome 2019-03-06 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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.
Invitae RCV000199801 SCV000254385 benign Hereditary nonpolyposis colorectal neoplasms 2024-01-27 criteria provided, single submitter clinical testing
GeneDx RCV000656877 SCV000565194 uncertain significance not provided 2022-11-16 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 29338072, 29596542, 30212499, 31159747, 34875107)
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000656877 SCV000601434 uncertain significance not provided 2020-06-25 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000129044 SCV000684938 uncertain significance Hereditary cancer-predisposing syndrome 2023-04-06 criteria provided, single submitter clinical testing This missense variant replaces leucine with valine at codon 488 of the MSH2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). This variant does not impact MSH2 function in a 6-thioguanine sensitivity assay in haploid human cells (internally defined LOF score threshold <= -1.32, PMID: 33357406). This variant has been reported in an individual referred for hereditary cancer screening (PMID: 31159747). This variant has been identified in 6/251314 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Counsyl RCV000662760 SCV000785554 uncertain significance Lynch syndrome 1 2017-09-13 criteria provided, single submitter clinical testing
GeneKor MSA RCV000129044 SCV000822044 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-01 criteria provided, single submitter clinical testing
Mendelics RCV000662760 SCV001135731 uncertain significance Lynch syndrome 1 2019-05-28 criteria provided, single submitter clinical testing
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden RCV000656877 SCV002009343 uncertain significance not provided 2021-11-03 criteria provided, single submitter clinical testing
Myriad Genetics, Inc. RCV000662760 SCV004018301 benign Lynch syndrome 1 2023-03-20 criteria provided, single submitter clinical testing This variant is considered benign. This variant has been observed in trans with a known pathogenic variant in one or more individuals lacking clinical features consistent with gene-specific recessive disease. This variant is strongly associated with less severe personal and family histories of cancer, typical for individuals without pathogenic variants in this gene [PMID: 25085752].
Baylor Genetics RCV000662760 SCV004196226 uncertain significance Lynch syndrome 1 2023-09-29 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV003997475 SCV004833396 uncertain significance Lynch syndrome 2023-12-13 criteria provided, single submitter clinical testing This missense variant replaces leucine with valine at codon 488 of the MSH2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). This variant does not impact MSH2 function in a 6-thioguanine sensitivity assay in haploid human cells (internally defined LOF score threshold <= -1.32, PMID: 33357406). This variant has been reported in an individual referred for hereditary cancer screening (PMID: 31159747). This variant has been identified in 6/251314 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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