ClinVar Miner

Submissions for variant NM_006939.4(SOS2):c.3744G>T (p.Trp1248Cys) (rs138133010)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000537448 SCV000656027 likely benign Noonan syndrome 9 2020-12-06 criteria provided, single submitter clinical testing
GeneDx RCV000613957 SCV000714769 benign not specified 2017-04-13 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000613957 SCV001361615 benign not specified 2019-09-01 criteria provided, single submitter clinical testing Variant summary: SOS2 c.3744G>T (p.Trp1248Cys) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00049 in 251468 control chromosomes. The observed variant frequency is approximately 195 fold of the estimated maximal expected allele frequency for a pathogenic variant in SOS2 causing Noonan Syndrome and Related Conditions phenotype (2.5e-06), strongly suggesting that the variant is benign. c.3744G>T has been reported in the literature in sequencing studies of individuals affected with Rasopathies (Cordeddu_2015). These report(s) do not provide unequivocal conclusions about association of the variant with Noonan Syndrome and Related Conditions. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign (n=1)/likely benign(n=1). Based on the evidence outlined above, the variant was classified as benign.

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