ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.2189A>G (p.Tyr730Cys)

gnomAD frequency: 0.00001  dbSNP: rs587782900
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000132542 SCV000187639 uncertain significance Hereditary cancer-predisposing syndrome 2022-10-21 criteria provided, single submitter clinical testing The p.Y730C variant (also known as c.2189A>G), located in coding exon 4 of the MSH6 gene, results from an A to G substitution at nucleotide position 2189. The tyrosine at codon 730 is replaced by cysteine, an amino acid with highly dissimilar properties. This alteration was detected in 1/1893 unselected ovarian cancer patients and has an Align-GVGD score of C0 which is predicted to be less likely to impact protein function (Pal T et al. Br J Cancer. 2012; 107:1783-90). This amino acid position is poorly 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV002228511 SCV000551173 benign Hereditary nonpolyposis colorectal neoplasms 2024-04-20 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000132542 SCV000908255 uncertain significance Hereditary cancer-predisposing syndrome 2023-09-06 criteria provided, single submitter clinical testing This missense variant replaces tyrosine with cysteine at codon 730 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 been reported in an individual with ovarian cancer (PMID: 23047549). This variant has been identified in 2/250940 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 RCV003998152 SCV004836174 uncertain significance Lynch syndrome 2023-10-02 criteria provided, single submitter clinical testing This missense variant replaces tyrosine with cysteine at codon 730 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 been reported in an individual with ovarian cancer (PMID: 23047549). This variant has been identified in 2/250940 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.
Baylor Genetics RCV004567156 SCV005054822 uncertain significance Endometrial carcinoma 2024-03-25 criteria provided, single submitter clinical testing

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