Submissions for variant NM_000179.3(MSH6):c.3968T>C (p.Phe1323Ser)

gnomAD frequency: 0.00003  dbSNP: rs1051564593

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000491517	SCV000580283	uncertain significance	Hereditary cancer-predisposing syndrome	2023-01-04	criteria provided, single submitter	clinical testing	The p.F1323S variant (also known as c.3968T>C), located in coding exon 9 of the MSH6 gene, results from a T to C substitution at nucleotide position 3968. The phenylalanine at codon 1323 is replaced by serine, an amino acid with highly 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.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000759147	SCV000888284	uncertain significance	not provided	2019-04-18	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000491517	SCV000906771	uncertain significance	Hereditary cancer-predisposing syndrome	2023-09-06	criteria provided, single submitter	clinical testing	This missense variant replaces phenylalanine with serine at codon 1323 in the MSH6 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with breast cancer (PMID: 36200007). This variant has been identified in 1/31372 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.
Invitae	RCV000797850	SCV000937434	likely benign	Hereditary nonpolyposis colorectal neoplasms	2023-03-31	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV003316642	SCV004020117	likely benign	Lynch syndrome 5	2023-11-14	criteria provided, single submitter	clinical testing	This variant is considered likely benign. This variant is strongly associated with less severe personal and family histories of cancer, typical for individuals without pathogenic variants in this gene [PMID: 27363726].
Baylor Genetics	RCV003464057	SCV004195682	uncertain significance	Endometrial carcinoma	2023-07-04	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV004003460	SCV004835178	uncertain significance	Lynch syndrome	2023-11-10	criteria provided, single submitter	clinical testing	This missense variant replaces phenylalanine with serine at codon 1323 in the MSH6 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with breast cancer (PMID: 36200007). This variant has been identified in 1/31372 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.