ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.131C>T (p.Pro44Leu)

gnomAD frequency: 0.00001  dbSNP: rs863224615
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000198916 SCV000254273 likely benign Hereditary nonpolyposis colorectal neoplasms 2024-01-09 criteria provided, single submitter clinical testing
Ambry Genetics RCV000570887 SCV000673946 likely benign Hereditary cancer-predisposing syndrome 2016-04-01 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.
Color Diagnostics, LLC DBA Color Health RCV000570887 SCV000690194 uncertain significance Hereditary cancer-predisposing syndrome 2023-04-20 criteria provided, single submitter clinical testing This missense variant replaces proline with leucine at codon 44 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 reported for this variant. This variant has not been reported in individuals affected with MSH6-related disorders in the literature. This variant has been identified in 1/31326 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 RCV003996992 SCV004827986 uncertain significance Lynch syndrome 2023-05-04 criteria provided, single submitter clinical testing This missense variant replaces proline with leucine at codon 44 of the MSH6 protein. Computational prediction tools and conservation analyses suggest that this variant may not impact the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/31326 chromosomes in the general population by the Genome Aggregation Database (gnomAD). 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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