ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.3383A>G (p.Tyr1128Cys)

gnomAD frequency: 0.00001  dbSNP: rs587779261
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000524174 SCV000551208 benign Hereditary nonpolyposis colorectal neoplasms 2023-11-19 criteria provided, single submitter clinical testing
Ambry Genetics RCV000573399 SCV000670003 uncertain significance Hereditary cancer-predisposing syndrome 2022-12-22 criteria provided, single submitter clinical testing The p.Y1128C variant (also known as c.3383A>G), located in coding exon 5 of the MSH6 gene, results from an A to G substitution at nucleotide position 3383. The tyrosine at codon 1128 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Color Diagnostics, LLC DBA Color Health RCV000573399 SCV000690348 uncertain significance Hereditary cancer-predisposing syndrome 2023-07-21 criteria provided, single submitter clinical testing This missense variant replaces tyrosine with cysteine at codon 1128 of the MSH6 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). 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 3/282828 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001800369 SCV002046334 uncertain significance not provided 2020-10-25 criteria provided, single submitter clinical testing
Baylor Genetics RCV003460682 SCV004195659 uncertain significance Endometrial carcinoma 2023-07-14 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV003997088 SCV004835060 uncertain significance Lynch syndrome 2023-08-15 criteria provided, single submitter clinical testing This missense variant replaces tyrosine with cysteine at codon 1128 of the MSH6 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). 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 3/282828 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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