Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002785989 | SCV003022984 | uncertain significance | RASopathy | 2022-07-11 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 1267 of the SOS1 protein (p.His1267Tyr). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with SOS1-related conditions. This variant is not present in population databases (gnomAD no frequency). |
Ambry Genetics | RCV003167761 | SCV003863129 | uncertain significance | Cardiovascular phenotype | 2022-12-06 | criteria provided, single submitter | clinical testing | The p.H1267Y variant (also known as c.3799C>T), located in coding exon 23 of the SOS1 gene, results from a C to T substitution at nucleotide position 3799. The histidine at codon 1267 is replaced by tyrosine, an amino acid with similar properties. This amino acid position is conserved. 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. |