Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
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, |
RCV000038555 | SCV000062233 | uncertain significance | not specified | 2009-04-21 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
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. |
Gene |
RCV002221483 | SCV002499017 | likely benign | not provided | 2021-10-11 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000523675 | SCV003447166 | likely benign | RASopathy | 2023-11-13 | criteria provided, single submitter | clinical testing | |
Prevention |
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). |