ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.23C>T (p.Thr8Met) (rs17217716)

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Total submissions: 18
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000076466 SCV000107495 no known pathogenicity Lynch syndrome 2013-09-05 reviewed by expert panel research Multifactorial likelihood analysis posterior probability <0.001
Invitae RCV001082308 SCV000166272 benign Hereditary nonpolyposis colorectal neoplasms 2020-12-04 criteria provided, single submitter clinical testing
GeneDx RCV000434381 SCV000170341 benign not provided 2018-11-15 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 30333958, 21681552, 22290698, 25371881, 23760103, 24728327, 10777691, 26332594, 21615986, 15340835, 15849733, 16810763, 18383312, 26951660, 28580595, 30998989, 31237724)
Ambry Genetics RCV000130682 SCV000185569 benign Hereditary cancer-predisposing syndrome 2014-09-03 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.
Illumina Clinical Services Laboratory,Illumina RCV000144624 SCV000430908 likely benign Lynch syndrome I 2018-03-06 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000434381 SCV000511017 benign not provided 2017-02-09 criteria provided, single submitter clinical testing
Color Health, Inc RCV000130682 SCV000685038 benign Hereditary cancer-predisposing syndrome 2015-03-05 criteria provided, single submitter clinical testing
Center for Human Genetics, Inc,Center for Human Genetics, Inc RCV000144624 SCV000781766 uncertain significance Lynch syndrome I 2016-11-01 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000121556 SCV000806029 benign not specified 2017-06-15 criteria provided, single submitter clinical testing
Mendelics RCV000144624 SCV001135688 benign Lynch syndrome I 2019-05-28 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000121556 SCV001156593 benign not specified 2018-09-21 criteria provided, single submitter clinical testing
ITMI RCV000121556 SCV000085750 not provided not specified 2013-09-19 no assertion provided reference population
Pathway Genomics RCV000144624 SCV000189951 likely benign Lynch syndrome I 2014-07-24 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001353559 SCV000592449 likely benign Carcinoma of colon no assertion criteria provided clinical testing The p.Thr8Met variant has been identified in 7/4128 proband chromsomes in individuals with Lynch syndrome, and was also identified in 2/200 control chromosomes (Ali 2012, Chao 2008, Mangold 2005, Nomura 2000, Valentin 2011, Wang 2006, Wei 2011), increasing the likelihood that this is a benign variant. The variant has also been reported in the HGMD, LOVD and several colon cancer databases, some of which suggest that it is probably neutral. It is listed in the dbSNP database as coming from a "clinical source" (ID#: rs17217716) with a MAF score of 0.008 (1000 Genomes) and it is observed at low frequency in the Han Chinese and Japanese HapMap population samples, increasing the likelihood this variant may be a common low frequency variant with no clinical significance. The p.Thr8 residue is conserved across mammals but computational analyses (SIFT, AlignGVGD) provide inconsistent predictions regarding the impact to the protein. However, this information is not predictive enough to rule out pathogenicity. In summary, the clinical significance of this variant cannot be determined with certainty at this time, although we would lean towards a more benign role for this variant. This variant is classified as Predicted Benign.
Mayo Clinic Laboratories, Mayo Clinic RCV000121556 SCV000691894 likely benign not specified no assertion criteria provided clinical testing
True Health Diagnostics RCV000130682 SCV000788032 likely benign Hereditary cancer-predisposing syndrome 2018-03-02 no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center RCV000121556 SCV001809338 benign not specified no assertion criteria provided clinical testing
Human Genetics - Radboudumc,Radboudumc RCV000121556 SCV001953189 benign not specified no assertion criteria provided clinical testing

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