Submissions for variant NM_000179.3(MSH6):c.114del (p.Ala40fs)

dbSNP: rs1558644995

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Color Diagnostics, LLC DBA Color Health	RCV000773559	SCV000907253	pathogenic	Hereditary cancer-predisposing syndrome	2020-01-15	criteria provided, single submitter	clinical testing	This variant deletes 1 nucleotide in exon 1 of the MSH6 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of MSH6 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Ambry Genetics	RCV000773559	SCV002617647	pathogenic	Hereditary cancer-predisposing syndrome	2022-04-12	criteria provided, single submitter	clinical testing	The c.114delC pathogenic mutation, located in coding exon 1 of the MSH6 gene, results from a deletion of one nucleotide at nucleotide position 114, causing a translational frameshift with a predicted alternate stop codon (p.A40Pfs*41). 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.
Myriad Genetics, Inc.	RCV003453597	SCV004185849	pathogenic	Lynch syndrome 5	2023-08-09	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
Laboratory for Genotyping Development, RIKEN	RCV003166045	SCV002758357	pathogenic	Gastric cancer	2021-07-01	no assertion criteria provided	research