ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.589G>C (p.Asp197His)

dbSNP: rs148517241
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000630129 SCV000751085 benign Hereditary nonpolyposis colorectal neoplasms 2023-11-28 criteria provided, single submitter clinical testing
Ambry Genetics RCV001024658 SCV001186713 uncertain significance Hereditary cancer-predisposing syndrome 2019-05-13 criteria provided, single submitter clinical testing The p.D197H variant (also known as c.589G>C), located in coding exon 3 of the MSH6 gene, results from a G to C substitution at nucleotide position 589. The aspartic acid at codon 197 is replaced by histidine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. In addition, the CoDP in silico tool predicts this alteration to have minor impact on molecular function, with a score of 0.001 (Terui H et al. J. Biomed. Sci. 2013 Apr;20:25). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002483771 SCV002790154 uncertain significance Endometrial carcinoma; Lynch syndrome 5; Mismatch repair cancer syndrome 3 2021-11-08 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV004002791 SCV004841071 uncertain significance Lynch syndrome 2023-05-30 criteria provided, single submitter clinical testing This missense variant replaces aspartic acid with histidine at codon 197 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 1/251398 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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