Submissions for variant NM_000179.3(MSH6):c.2951A>C (p.Asn984Thr)

gnomAD frequency: 0.00001  dbSNP: rs587779927

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000115396	SCV000149305	uncertain significance	not provided	2024-01-03	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 17531815, 21120944)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000204834	SCV000261024	benign	Hereditary nonpolyposis colorectal neoplasms	2025-01-30	criteria provided, single submitter	clinical testing
Counsyl	RCV000409319	SCV000489729	uncertain significance	Lynch syndrome 5	2016-11-11	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV001017633	SCV001178742	uncertain significance	Hereditary cancer-predisposing syndrome	2023-04-14	criteria provided, single submitter	clinical testing	The p.N984T variant (also known as c.2951A>C), located in coding exon 4 of the MSH6 gene, results from an A to C substitution at nucleotide position 2951. The asparagine at codon 984 is replaced by threonine, an amino acid with similar properties. 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.
Myriad Genetics, Inc.	RCV000409319	SCV004019020	uncertain significance	Lynch syndrome 5	2023-03-29	criteria provided, single submitter	clinical testing	This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk.
Color Diagnostics, LLC DBA Color Health	RCV001017633	SCV004357685	uncertain significance	Hereditary cancer-predisposing syndrome	2023-02-27	criteria provided, single submitter	clinical testing	This missense variant replaces asparagine with threonine at codon 984 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.