ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.1168C>T (p.Leu390Phe) (rs17224367)

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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000115495 SCV000172768 benign Hereditary cancer-predisposing syndrome 2014-08-11 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Seen in trans with a mutation or in homozygous state in individual without severe disease for that gene
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000034549 SCV000043339 variant of unknown significance not provided 2012-07-13 no assertion criteria provided research Converted during submission to Uncertain significance.
Color RCV000115495 SCV000684912 benign Hereditary cancer-predisposing syndrome 2015-04-09 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000078420 SCV000110269 benign not specified 2013-02-19 criteria provided, single submitter clinical testing
GeneDx RCV000078420 SCV000149404 benign not specified 2018-02-20 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
ITMI RCV000078420 SCV000085763 not provided not specified 2013-09-19 no assertion provided reference population
Illumina Clinical Services Laboratory,Illumina RCV000076053 SCV000430923 likely benign Lynch syndrome 2016-06-14 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000034549 SCV000696199 benign not provided 2016-03-21 criteria provided, single submitter clinical testing Variant summary: The c.1168C>T variant affects a non-conserved nucleotide, resulting in amino acid change from Leu to Phe. 2/4 in-silico tools predict this variant to be benign (SNPs&GO not captured due to low reliability index). This variant is found in 229/123604 control chromosomes (2 homozygotes) at a frequency of 0.0018527. The frequency of this variant in East Asian control population is 0.0217, which is about 38 times of the maximal expected frequency of a pathogenic allele (0.0005683), suggesting this variant is benign. This variant has been reported in a large number of patients with LS or endometrial cancer. Two co-occurrences with a pathogenic variant (MLH1, c.2157dup, p.Val720Cysfs*3 and MSH2 c.196-187dupG, respectively) were reported, along with a reported lack of co-segregation with the disease (Okamura_1998). Multiple functional studies showed that MSH2 p.L390F has similar activity to wild-type MSH2. In addition, multiple clinical laboratories/reputable databases classified this variant as benign. Taken together, this variant was classified as benign.
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000076053 SCV000107066 no known pathogenicity Lynch syndrome 2013-09-05 reviewed by expert panel research Multifactorial likelihood analysis posterior probability <0.001
Invitae RCV000524333 SCV000261493 benign Hereditary nonpolyposis colon cancer 2018-01-03 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000078420 SCV000539680 likely benign not specified 2016-03-28 criteria provided, single submitter clinical testing Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: 2.1% in East Asian population with 2 homozygotes.
PreventionGenetics RCV000078420 SCV000805991 benign not specified 2017-04-04 criteria provided, single submitter clinical testing

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