ClinVar Miner

Submissions for variant NM_005633.4(SOS1):c.3709C>A (p.Pro1237Thr)

dbSNP: rs371408734
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen RASopathy Variant Curation Expert Panel RCV000523675 SCV000616503 likely benign RASopathy 2017-04-18 reviewed by expert panel curation The filtering allele frequency of the c.3709C>A (p.Pro1237Thr) variant in the SOS1 gene is 0.0373% (11/16510) of South Asian chromosomes by the Exome Aggregation Consortium, which is a high enough frequency to be classified as likely benign based on thresholds defined by the ClinGen RASopathy Expert Panel (BS1; PMID:29493581)
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000038555 SCV000062233 uncertain significance not specified 2009-04-21 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000038555 SCV001821488 likely benign not specified 2021-08-09 criteria provided, single submitter clinical testing Variant summary: SOS1 c.3709C>A (p.Pro1237Thr) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0001 in 251126 control chromosomes in the gnomAD database, including 1 homozygote. The observed variant frequency is approximately 3.45 fold of the estimated maximal expected allele frequency for a pathogenic variant in SOS1 causing Noonan Syndrome phenotype (3e-05), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.3709C>A in individuals affected with Noonan Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. One expert panel (ClinGen RASopathy Variant Curation Expert Panel) has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as likely benign.
GeneDx RCV002221483 SCV002499017 likely benign not provided 2021-10-11 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000523675 SCV003447166 likely benign RASopathy 2023-11-13 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004742237 SCV005362628 likely benign SOS1-related disorder 2024-08-14 no assertion criteria provided clinical testing This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

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