ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.334A>G (p.Asn112Asp)

dbSNP: rs864622397
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000204549 SCV000260470 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2024-01-03 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 112 of the MSH6 protein (p.Asn112Asp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with breast cancer (PMID: 35264596). ClinVar contains an entry for this variant (Variation ID: 220150). 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 with a negative predictive value of 95%. 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.
Ambry Genetics RCV000491364 SCV000580297 uncertain significance Hereditary cancer-predisposing syndrome 2022-07-07 criteria provided, single submitter clinical testing The p.N112D variant (also known as c.334A>G), located in coding exon 2 of the MSH6 gene, results from an A to G substitution at nucleotide position 334. The asparagine at codon 112 is replaced by aspartic acid, an amino acid with highly similar 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 RCV000491364 SCV000690346 uncertain significance Hereditary cancer-predisposing syndrome 2023-12-06 criteria provided, single submitter clinical testing This missense variant replaces asparagine with aspartic acid at codon 112 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 not been identified 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.
Mendelics RCV003491957 SCV001135780 likely benign Hereditary cancer 2024-01-23 criteria provided, single submitter clinical testing
GeneDx RCV001753613 SCV002005715 uncertain significance not provided 2019-10-15 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV003493500 SCV004243577 uncertain significance not specified 2024-02-06 criteria provided, single submitter clinical testing
Molecular Oncology - Human Genetics Lab, University of Sao Paulo RCV001843493 SCV002103117 uncertain significance Hepatoblastoma no assertion criteria provided research

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