Submissions for variant NM_000179.3(MSH6):c.4068_4071dup (p.Lys1358delinsAspTer)

dbSNP: rs55740729

Total submissions: 24

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT)	RCV000074986	SCV000108202	likely benign	Lynch syndrome	2013-09-05	reviewed by expert panel	research	MAF >1% in specific ethnic group
GeneDx	RCV000115430	SCV000149339	likely benign	Hereditary cancer-predisposing syndrome	2014-10-07	criteria provided, single submitter	clinical testing	The variant is found in HEREDICANCER,BR-OV-HEREDIC,COLO-HEREDIC panel(s).
Ambry Genetics	RCV000115430	SCV000184313	benign	Hereditary cancer-predisposing syndrome	2015-06-04	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Invitae	RCV001081385	SCV000262375	benign	Hereditary nonpolyposis colorectal neoplasms	2024-02-01	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000074986	SCV000430982	likely benign	Lynch syndrome	2016-06-14	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000121569	SCV000592669	benign	not specified	2017-05-29	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000115430	SCV000685486	benign	Hereditary cancer-predisposing syndrome	2015-02-19	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000587315	SCV000695913	benign	not provided	2016-03-21	criteria provided, single submitter	clinical testing	Variant summary: The c.4068_4071dupGATT (legacy name c.4065_4066insTTGA) variant results in a termination codon only two amino acids before the normal stop codon, thus the mutated protein may still retain its function, which was supported by one functional study (Martinez_2010). One in-silico tool predicts damaging outcome for this variant. This variant is found in 272/8626 control chromosomes in East Asian population (5 homozygotes) at a frequency of 0.0315, which is about 221 times of the maximal expected frequency of a pathogenic allele (0.0001421), suggesting this variant is benign. In addition, multiple clinical laboratories/reputable databases classified this variant as benign/likely benign. Taken together, this variant was classified as benign.
PreventionGenetics, part of Exact Sciences	RCV000587315	SCV000805903	likely benign	not provided	2017-03-21	criteria provided, single submitter	clinical testing
Mendelics	RCV003228794	SCV000837938	benign	Hereditary nonpolyposis colon cancer	2023-08-22	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000121569	SCV000888287	benign	not specified	2021-03-11	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000121569	SCV002070936	benign	not specified	2019-04-20	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000115430	SCV002536316	benign	Hereditary cancer-predisposing syndrome	2020-06-10	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000121569	SCV002552386	likely benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003149727	SCV003838334	benign	Breast and/or ovarian cancer	2022-02-07	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV003315590	SCV004016000	likely benign	Lynch syndrome 5	2023-07-07	criteria provided, single submitter	clinical testing
ITMI	RCV000121569	SCV000085765	not provided	not specified	2013-09-19	no assertion provided	reference population
3DMed Clinical Laboratory Inc	RCV000677891	SCV000804052	likely benign	Sigmoid colon cancer	2017-05-15	no assertion criteria provided	clinical testing
Ding PR Lab, Sun Yat-sen University Cancer Center	RCV001093695	SCV001250879	uncertain significance	Lynch syndrome 1		no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000587315	SCV001742036	likely benign	not provided		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000587315	SCV001800573	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000587315	SCV001922852	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000587315	SCV001969050	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000587315	SCV001977735	likely benign	not provided		no assertion criteria provided	clinical testing