Submissions for variant NM_000251.3(MSH2):c.1236T>A (p.Asn412Lys)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002780558	SCV003027114	uncertain significance	Hereditary nonpolyposis colorectal neoplasms	2022-01-06	criteria provided, single submitter	clinical testing	In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt MSH2 protein function. This variant has not been reported in the literature in individuals affected with MSH2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 412 of the MSH2 protein (p.Asn412Lys).
Ambry Genetics	RCV004064715	SCV005033214	uncertain significance	Hereditary cancer-predisposing syndrome	2023-10-23	criteria provided, single submitter	clinical testing	The p.N412K variant (also known as c.1236T>A), located in coding exon 7 of the MSH2 gene, results from a T to A substitution at nucleotide position 1236. The asparagine at codon 412 is replaced by lysine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.