ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.1787A>G (p.Asn596Ser) (rs41295288)

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Total submissions: 13
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000115511 SCV000187001 benign Hereditary cancer-predisposing syndrome 2014-11-18 criteria provided, single submitter clinical testing
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000034554 SCV000043344 variant of unknown significance not provided 2012-07-13 no assertion criteria provided research Converted during submission to Uncertain significance.
CSER_CC_NCGL; University of Washington Medical Center RCV000148641 SCV000190356 uncertain significance Colorectal cancer, non-polyposis 2014-06-01 no assertion criteria provided research
CeGaT Praxis fuer Humangenetik Tuebingen RCV000034554 SCV000780663 uncertain significance not provided 2018-02-28 criteria provided, single submitter clinical testing
Center for Human Genetics, Inc RCV000659882 SCV000781774 uncertain significance Lynch syndrome I 2016-11-01 criteria provided, single submitter clinical testing
Color RCV000115511 SCV000902601 benign Hereditary cancer-predisposing syndrome 2015-11-05 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000765668 SCV000897010 uncertain significance Lynch syndrome I; Turcot syndrome; Muir-Torré syndrome 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000200985 SCV000149420 likely benign not specified 2018-01-02 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.
GeneKor MSA RCV000115511 SCV000822048 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-01 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000200985 SCV000917713 uncertain significance not specified 2018-07-19 criteria provided, single submitter clinical testing Variant summary: MSH2 c.1787A>G (p.Asn596Ser) results in a conservative amino acid change located in the DNA mismatch repair protein MutS, core domain of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00029 in 279664 control chromosomes (gnomAD and publications). This frequency is not significantly higher than expected for a pathogenic variant in MSH2 causing Lynch Syndrome (0.00029 vs 0.00057), allowing no conclusion about variant significance. c.1787A>G has been reported in the literature in individuals affected with Lynch Syndrome. A family with this variant suggests lack of segregation with the disease since one of the affected family members did not carry the variant, although four affected family members did carry the variant (Genuardi_1999). One publication indicates the variant co-occurred with a "familial MMR mutation (MSH6)" (Jori_2014). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as "benign/likely benign." Based on the available evidence outlined above, the variant was classified as VUS-possibly benign.
Invitae RCV000524361 SCV000153982 benign Hereditary nonpolyposis colon cancer 2018-01-02 criteria provided, single submitter clinical testing
Mendelics RCV000076286 SCV000837838 uncertain significance Lynch syndrome 2018-07-02 criteria provided, single submitter clinical testing
PreventionGenetics RCV000034554 SCV000806012 likely benign not provided 2017-10-27 criteria provided, single submitter clinical testing

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