Submissions for variant NM_000179.3(MSH6):c.1586G>T (p.Gly529Val)

dbSNP: rs786201964

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000164520	SCV000215172	uncertain significance	Hereditary cancer-predisposing syndrome	2023-08-16	criteria provided, single submitter	clinical testing	The p.G529V variant (also known as c.1586G>T), located in coding exon 4 of the MSH6 gene, results from a G to T substitution at nucleotide position 1586. The glycine at codon 529 is replaced by valine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae	RCV000204361	SCV000259340	likely benign	Hereditary nonpolyposis colorectal neoplasms	2023-11-28	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000164520	SCV000685204	uncertain significance	Hereditary cancer-predisposing syndrome	2023-12-06	criteria provided, single submitter	clinical testing	This missense variant replaces glycine with valine at codon 529 of the MSH6 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, 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 1/251358 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.
Sema4, Sema4	RCV000164520	SCV002535639	uncertain significance	Hereditary cancer-predisposing syndrome	2021-06-03	criteria provided, single submitter	curation
GeneDx	RCV003235082	SCV003933333	uncertain significance	not provided	2023-06-16	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 17531815, 21120944)
Baylor Genetics	RCV003462137	SCV004195603	uncertain significance	Endometrial carcinoma	2023-08-08	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV003995346	SCV004839528	uncertain significance	Lynch syndrome	2023-12-18	criteria provided, single submitter	clinical testing	This missense variant replaces glycine with valine at codon 529 of the MSH6 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, 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 1/251358 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.