Submissions for variant NM_000179.3(MSH6):c.3519_3522dup (p.Thr1175fs)

dbSNP: rs267608101

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT)	RCV000074876	SCV000108088	pathogenic	Lynch syndrome	2013-09-05	reviewed by expert panel	research	Coding sequence variation resulting in a stop codon
Myriad Genetics, Inc.	RCV003450972	SCV004185774	pathogenic	Lynch syndrome 5	2023-08-24	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
Ambry Genetics	RCV004019096	SCV005032889	pathogenic	Hereditary cancer-predisposing syndrome	2024-02-22	criteria provided, single submitter	clinical testing	The c.3519_3522dupGTTT pathogenic mutation, located in coding exon 6 of the MSH6 gene, results from a duplication of GTTT at nucleotide position 3519, causing a translational frameshift with a predicted alternate stop codon (p.T1175Vfs*3). This mutation was detected in a proband with colorectal cancer that demonstrated high microsatellite instability and loss of MSH6 staining by immunohistochemistry (IHC) (van Lier MG et al. J Pathol, 2012 Apr;226:764-74), and was also detected in 1/108 Dutch families with a clinical suspicion of Lynch syndrome (Ramsoekh D et al. Gut, 2008 Nov;57:1539-44). In addition to the clinical data presented in the literature, 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.
Mayo Clinic Laboratories, Mayo Clinic	RCV000201987	SCV000257261	pathogenic	not provided		no assertion criteria provided	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000201987	SCV000592647	pathogenic	not provided		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000201987	SCV002036721	pathogenic	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000201987	SCV002037695	pathogenic	not provided		no assertion criteria provided	clinical testing