Submissions for variant NM_000179.3(MSH6):c.2501G>A (p.Ser834Asn)

dbSNP: rs752544046

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000217167	SCV000275451	uncertain significance	Hereditary cancer-predisposing syndrome	2022-09-08	criteria provided, single submitter	clinical testing	The p.S834N variant (also known as c.2501G>A), located in coding exon 4 of the MSH6 gene, results from a G to A substitution at nucleotide position 2501. The serine at codon 834 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species, and asparagine is the reference amino acid in other 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.
Invitae	RCV000461932	SCV000551197	likely benign	Hereditary nonpolyposis colorectal neoplasms	2023-12-17	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000217167	SCV000908400	uncertain significance	Hereditary cancer-predisposing syndrome	2023-05-24	criteria provided, single submitter	clinical testing	This missense variant replaces serine with asparagine at codon 834 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 1/248568 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	RCV000985833	SCV001134412	uncertain significance	not provided	2019-12-17	criteria provided, single submitter	clinical testing
Mendelics	RCV002247652	SCV002518278	uncertain significance	not specified	2022-05-04	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV003462469	SCV004195638	uncertain significance	Endometrial carcinoma	2023-07-26	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV003997908	SCV004842504	uncertain significance	Lynch syndrome	2023-12-07	criteria provided, single submitter	clinical testing	This missense variant replaces serine with asparagine at codon 834 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 hereditary cancer in the literature. This variant has been observed together with a pathogenic truncation variant in the same gene in an individual affected with endometrial cancer (Color internal data). This variant has been identified in 1/248568 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.