Submissions for variant NM_000179.3(MSH6):c.2253T>C (p.Asn751=)

gnomAD frequency: 0.02003  dbSNP: rs2020913

Total submissions: 19

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT)	RCV000030262	SCV000107936	no known pathogenicity	Lynch syndrome	2013-09-05	reviewed by expert panel	research	MAF >1%
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000030262	SCV000052929	benign	Lynch syndrome	2011-08-18	criteria provided, single submitter	curation	Converted during submission to Benign.
Eurofins Ntd Llc (ga)	RCV000078310	SCV000110151	benign	not specified	2013-06-07	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000162399	SCV000212724	benign	Hereditary cancer-predisposing syndrome	2014-11-18	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, 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	RCV000757473	SCV000262398	benign	Hereditary nonpolyposis colorectal neoplasms	2024-02-01	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000078310	SCV000302870	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000625494	SCV000430970	benign	Lynch syndrome 5	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Color Diagnostics, LLC DBA Color Health	RCV000162399	SCV000685270	benign	Hereditary cancer-predisposing syndrome	2015-04-07	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000078310	SCV000885715	benign	not specified	2019-04-05	criteria provided, single submitter	clinical testing
GeneDx	RCV001618219	SCV001847613	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000078310	SCV002552308	benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003149586	SCV003837644	benign	Breast and/or ovarian cancer	2021-11-18	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000625494	SCV004015989	benign	Lynch syndrome 5	2023-07-07	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000078310	SCV000257221	benign	not specified		no assertion criteria provided	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001353756	SCV000592602	benign	Carcinoma of colon		no assertion criteria provided	clinical testing	The p.Asn751Asn variant is not expected to have clinical significance because it does not alter an amino acid residue and is not located near a splice site. In addition, this variant has been identified in dbSNP (rs2020913) as a polymorphism at about 1% frequency in a Yoruban cohort and in the exome variant server at an elevated frequency (~6 %) in African American individuals. In summary, based on this information this variant is considered benign. (it should be noted that the individual identified by our laboratory was indicated as "Black")
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000625494	SCV000745651	benign	Lynch syndrome 5	2016-04-06	no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000078310	SCV001797583	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV001618219	SCV001918509	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000078310	SCV001958668	benign	not specified		no assertion criteria provided	clinical testing