Submissions for variant NM_000251.3(MSH2):c.171_172del (p.Phe58fs)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV002398879	SCV002712914	pathogenic	Hereditary cancer-predisposing syndrome	2022-09-12	criteria provided, single submitter	clinical testing	The c.171_172delGT pathogenic mutation, located in coding exon 1 of the MSH2 gene, results from a deletion of two nucleotides at nucleotide positions 171 to 172, causing a translational frameshift with a predicted alternate stop codon (p.F58Qfs*23). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003759693	SCV004435175	pathogenic	Hereditary nonpolyposis colorectal neoplasms	2023-01-23	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. 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 creates a premature translational stop signal (p.Phe58Glnfs*23) in the MSH2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MSH2 are known to be pathogenic (PMID: 15849733, 24362816).