Submissions for variant NM_000179.3(MSH6):c.1869del (p.Gly624fs)

dbSNP: rs71539659

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT)	RCV000074694	SCV000107897	pathogenic	Lynch syndrome	2013-09-05	reviewed by expert panel	research	Coding sequence variation resulting in a stop codon
Ambry Genetics	RCV002408573	SCV002723463	pathogenic	Hereditary cancer-predisposing syndrome	2020-09-17	criteria provided, single submitter	clinical testing	The c.1869delC pathogenic mutation, located in coding exon 4 of the MSH6 gene, results from a deletion of one nucleotide at nucleotide position 1869, causing a translational frameshift with a predicted alternate stop codon (p.G624Afs*11). 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.	RCV003450934	SCV004185809	pathogenic	Lynch syndrome 5	2023-08-16	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
Invitae	RCV003593867	SCV004293907	pathogenic	Hereditary nonpolyposis colorectal neoplasms	2023-10-14	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gly624Alafs*11) in the MSH6 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MSH6 are known to be pathogenic (PMID: 18269114, 24362816). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Lynch syndrome (PMID: 20028993). ClinVar contains an entry for this variant (Variation ID: 89230). For these reasons, this variant has been classified as Pathogenic.