Submissions for variant NM_000251.3(MSH2):c.1064G>T (p.Arg355Ile)

dbSNP: rs730881754

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000160580	SCV000211171	uncertain significance	not provided	2014-09-09	criteria provided, single submitter	clinical testing	This variant is denoted MSH2 c.1064G>T at the cDNA level, p.Arg355Ile (R355I) at the protein level, and results in the change of an Arginine to an Isoleucine (AGA>ATA). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. MSH2 Arg355Ile was not observed at a significant allele frequency in the NHLBI Exome Sequencing Project. Since Arginine and Isoleucine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. MSH2 Arg355Ile occurs at a position that is highly conserved among mammals and is located in the Lever domain (Lutzen 2008). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available information, it is unclear whether MSH2 Arg355Ile is pathogenic or benign. We consider it to be a variant of uncertain significance.
Ambry Genetics	RCV002408719	SCV002717123	uncertain significance	Hereditary cancer-predisposing syndrome	2020-07-06	criteria provided, single submitter	clinical testing	The p.R355I variant (also known as c.1064G>T), located in coding exon 6 of the MSH2 gene, results from a G to T substitution at nucleotide position 1064. The arginine at codon 355 is replaced by isoleucine, an amino acid with similar properties. This amino acid position is well 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.