ClinVar Miner

Submissions for variant NM_005633.4(SOS1):c.746T>C (p.Ile249Thr)

dbSNP: rs1324979194
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000654921 SCV000776827 uncertain significance RASopathy 2022-08-22 criteria provided, single submitter clinical testing 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SOS1 protein function. ClinVar contains an entry for this variant (Variation ID: 543967). This missense change has been observed in individual(s) with clinical features of SOS1-related conditions (Invitae). This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 249 of the SOS1 protein (p.Ile249Thr).
Ambry Genetics RCV003163020 SCV003863127 uncertain significance Cardiovascular phenotype 2022-12-01 criteria provided, single submitter clinical testing The p.I249T variant (also known as c.746T>C), located in coding exon 6 of the SOS1 gene, results from a T to C substitution at nucleotide position 746. The isoleucine at codon 249 is replaced by threonine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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