Submissions for variant NM_000179.3(MSH6):c.3306T>A (p.Thr1102=)

gnomAD frequency: 0.00869  dbSNP: rs2020910

Total submissions: 22

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT)	RCV000030267	SCV000108048	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	RCV000030267	SCV000052934	benign	Lynch syndrome	2011-08-18	criteria provided, single submitter	curation	Converted during submission to Benign.
Eurofins Ntd Llc (ga)	RCV000078313	SCV000110156	benign	not specified	2013-02-19	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000162391	SCV000212711	benign	Hereditary cancer-predisposing syndrome	2019-05-07	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.
PreventionGenetics, part of Exact Sciences	RCV000078313	SCV000302877	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000625243	SCV000430975	benign	Lynch syndrome 5	2018-01-12	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	RCV000162391	SCV000537360	benign	Hereditary cancer-predisposing syndrome	2015-04-08	criteria provided, single submitter	clinical testing
Invitae	RCV000756348	SCV000561540	benign	Hereditary nonpolyposis colorectal neoplasms	2024-02-01	criteria provided, single submitter	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000625243	SCV000744298	benign	Lynch syndrome 5	2015-09-21	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000078313	SCV000884134	benign	not specified	2018-09-09	criteria provided, single submitter	clinical testing
GeneDx	RCV001668141	SCV001884663	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000162391	SCV002528011	benign	Hereditary cancer-predisposing syndrome	2021-05-11	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000078313	SCV002552337	benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000625243	SCV004015982	benign	Lynch syndrome 5	2023-07-07	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV000030267	SCV004835045	benign	Lynch syndrome	2024-02-05	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000078313	SCV000257249	benign	not specified		no assertion criteria provided	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001353933	SCV000592634	benign	Carcinoma of colon		no assertion criteria provided	clinical testing	The p.Thr1102Thr variant has been identified in 27 out of 966 proband chromosomes (frequency 0.028) in individuals with breast, prostate and colorectal cancers, however no normal population controls were included in these studies (Chan 1999, Kolodner 1999, Vahteristo 2005, Colley 2005, Damaraju 2006). However, this variant is listed in dbSNP database (ID#: rs2020910) with an average heterozygosity of 0.053+/-0.154, increasing the likelihood that this variant is benign. In addition, this variant is not expected to have clinical significance because it does not alter an amino acid residue, and is not located near a splice junction. In summary, based on the above information this variant is classified as Benign.
True Health Diagnostics	RCV000162391	SCV000788049	likely benign	Hereditary cancer-predisposing syndrome	2018-02-15	no assertion criteria provided	clinical testing
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	RCV000078313	SCV001906244	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000078313	SCV001924653	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000078313	SCV001959169	benign	not specified		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000078313	SCV002036257	benign	not specified		no assertion criteria provided	clinical testing