ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.1078A>G (p.Ser360Gly)

gnomAD frequency: 0.00001  dbSNP: rs145994565
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001704606 SCV000568178 uncertain significance not provided 2023-06-06 criteria provided, single submitter clinical testing Observed in an individual with thyroid cancer (Yehia et al., 2018); In silico analysis supports that this missense variant does not alter protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 23621914, 21437237, 29684080, 30267214)
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001704606 SCV000601502 uncertain significance not provided 2022-12-23 criteria provided, single submitter clinical testing The frequency of this variant in the general population, 0.000016 (4/251160 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. In the published literature, the variant has been reported in one or more individual(s) with thyroid cancer (PMID: 29684080 (2018)) and breast cancer (PMID: 33471991 (2021); LOVD3 Shared (https://databases.lovd.nl/shared/)). 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 benign. Based on the available information, we are unable to determine the clinical significance of this variant.
Ambry Genetics RCV000563224 SCV000662405 likely benign Hereditary cancer-predisposing syndrome 2023-05-05 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV000629709 SCV000750665 likely benign Hereditary nonpolyposis colorectal neoplasms 2024-12-18 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000563224 SCV000911254 uncertain significance Hereditary cancer-predisposing syndrome 2023-03-15 criteria provided, single submitter clinical testing This missense variant replaces serine with glycine at codon 360 of the MSH6 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been performed for this variant. This variant has been reported in an individual affected with thyroid cancer (PMID: 29684080). This variant has been identified in 4/251160 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.
All of Us Research Program, National Institutes of Health RCV004003316 SCV004837647 uncertain significance Lynch syndrome 2024-08-06 criteria provided, single submitter clinical testing This missense variant replaces serine with glycine at codon 360 of the MSH6 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has been reported in an individual affected with thyroid cancer (PMID: 29684080). This variant has been identified in 4/251160 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.
Department of Pathology and Laboratory Medicine, Sinai Health System RCV005398691 SCV006052966 uncertain significance Endometrial carcinoma; Lynch syndrome 5; Mismatch repair cancer syndrome 3 2024-07-08 criteria provided, single submitter clinical testing

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