Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000159185 | SCV000209131 | likely benign | not provided | 2021-01-29 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge |
Labcorp Genetics |
RCV000461078 | SCV000553265 | likely benign | RASopathy | 2023-12-21 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001375569 | SCV001572456 | likely benign | not specified | 2021-04-05 | criteria provided, single submitter | clinical testing | Variant summary: SOS1 c.3946C>G (p.His1316Asp) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00011 in 251318 control chromosomes (gnomAD). The observed variant frequency is approximately 3.7 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.3946C>G in individuals affected with Noonan Syndrome and no experimental evidence demonstrating its impact on protein function have 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 uncertain significance. Based on the evidence outlined above, the variant was classified as likely benign. |
Ambry Genetics | RCV002372039 | SCV002624414 | uncertain significance | Cardiovascular phenotype | 2022-09-14 | criteria provided, single submitter | clinical testing | The p.H1316D variant (also known as c.3946C>G), located in coding exon 23 of the SOS1 gene, results from a C to G substitution at nucleotide position 3946. The histidine at codon 1316 is replaced by aspartic acid, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |