Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV001703448 | SCV000209062 | likely benign | not provided | 2020-12-29 | criteria provided, single submitter | clinical testing | This variant is associated with the following publications: (PMID: 30050098, 29907801) |
Labcorp Genetics |
RCV000231740 | SCV000288967 | likely benign | RASopathy | 2023-11-28 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000159118 | SCV001361137 | likely benign | not specified | 2024-02-15 | criteria provided, single submitter | clinical testing | Variant summary: SOS1 c.3729C>G (p.Asp1243Glu) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 7.3e-05 in 1613758 control chromosomes (gnomAD). The observed variant frequency is approximately 2.4 fold of the estimated maximal expected allele frequency for a pathogenic variant in SOS1 causing Noonan Syndrome And Related Conditions phenotype (3e-05), strongly suggesting that the variant is benign. c.3729C>G has been reported in the literature in a prenatal sample with cystic hygroma without strong evidence for causality (Leach_2019). This report does 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. The following publication has been ascertained in the context of this evaluation (PMID: 29907801). ClinVar contains an entry for this variant (Variation ID: 40734). Based on the evidence outlined above, the variant was classified as likely benign. |
Genome Diagnostics Laboratory, |
RCV001813302 | SCV002060655 | likely benign | Noonan syndrome and Noonan-related syndrome | 2016-12-12 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002345265 | SCV002621166 | uncertain significance | Cardiovascular phenotype | 2022-04-12 | criteria provided, single submitter | clinical testing | The p.D1243E variant (also known as c.3729C>G), located in coding exon 23 of the SOS1 gene, results from a C to G substitution at nucleotide position 3729. The aspartic acid at codon 1243 is replaced by glutamic acid, an amino acid with highly similar properties. This alteration has been reported in a prenatal subject with cystic hygroma (Leach NT et al. Genet Med, 2019 02;21:417-425). This amino acid position is not well conserved in available vertebrate species, and glutamic acid is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Prevention |
RCV004742234 | SCV005361771 | uncertain significance | SOS1-related disorder | 2024-05-21 | no assertion criteria provided | clinical testing | The SOS1 c.3729C>G variant is predicted to result in the amino acid substitution p.Asp1243Glu. This variant has been reported in a fetus with cystic hygroma; however, the authors suspected the variant was possibly benign (Table S2, Leach et al. 2019. PubMed ID: 29907801). This variant is reported in 0.010% of alleles in individuals of European (Non-Finnish) descent in gnomAD, which may be too common to be pathogenic (Gelb et al. 2018. PubMed ID 29493581). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |