ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.1264G>A (p.Asp422Asn)

dbSNP: rs1423874192
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001010627 SCV001170853 uncertain significance Hereditary cancer-predisposing syndrome 2019-03-02 criteria provided, single submitter clinical testing The p.D422N variant (also known as c.1264G>A), located in coding exon 4 of the MSH6 gene, results from a G to A substitution at nucleotide position 1264. The aspartic acid at codon 422 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. In addition, the CoDP in silico tool predicts this alteration to have minor impact on molecular function, with a score of 0.161 (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.
Invitae RCV001236507 SCV001409233 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2023-03-21 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 818734). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt MSH6 protein function. This variant has not been reported in the literature in individuals affected with MSH6-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 422 of the MSH6 protein (p.Asp422Asn).
Sema4, Sema4 RCV001010627 SCV002535616 uncertain significance Hereditary cancer-predisposing syndrome 2021-12-13 criteria provided, single submitter curation
All of Us Research Program, National Institutes of Health RCV004004487 SCV004827031 uncertain significance Lynch syndrome 2023-04-27 criteria provided, single submitter clinical testing

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