Submissions for variant NM_000179.3(MSH6):c.2615T>C (p.Ile872Thr)

gnomAD frequency: 0.00001  dbSNP: rs1064793342

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000487290	SCV000565867	uncertain significance	not provided	2024-06-06	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter 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)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000552497	SCV000624779	benign	Hereditary nonpolyposis colorectal neoplasms	2024-12-23	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000567884	SCV000662377	uncertain significance	Hereditary cancer-predisposing syndrome	2024-02-09	criteria provided, single submitter	clinical testing	The p.I872T variant (also known as c.2615T>C), located in coding exon 4 of the MSH6 gene, results from a T to C substitution at nucleotide position 2615. The isoleucine at codon 872 is replaced by threonine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this alteration remains unclear.
Color Diagnostics, LLC DBA Color Health	RCV000567884	SCV000911268	uncertain significance	Hereditary cancer-predisposing syndrome	2023-05-11	criteria provided, single submitter	clinical testing	This missense variant replaces isoleucine with threonine at codon 872 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 identified in 2/250062 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.
Baylor Genetics	RCV003470530	SCV004197602	uncertain significance	Endometrial carcinoma	2023-10-20	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV004002264	SCV004838327	uncertain significance	Lynch syndrome	2024-03-24	criteria provided, single submitter	clinical testing	This missense variant replaces isoleucine with threonine at codon 872 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 identified in 2/250062 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.