ClinVar Miner

Submissions for variant NM_005633.4(SOS1):c.464A>G (p.Tyr155Cys)

gnomAD frequency: 0.00001  dbSNP: rs1188280924
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001945099 SCV002180170 uncertain significance RASopathy 2021-06-28 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. 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with SOS1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces tyrosine with cysteine at codon 155 of the SOS1 protein (p.Tyr155Cys). The tyrosine residue is moderately conserved and there is a large physicochemical difference between tyrosine and cysteine.
Ambry Genetics RCV002334881 SCV002640292 uncertain significance Cardiovascular phenotype 2021-09-07 criteria provided, single submitter clinical testing The p.Y155C variant (also known as c.464A>G), located in coding exon 4 of the SOS1 gene, results from an A to G substitution at nucleotide position 464. The tyrosine at codon 155 is replaced by cysteine, an amino acid with highly dissimilar 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.
Genome-Nilou Lab RCV002468354 SCV002763576 uncertain significance Noonan syndrome 4 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV002468353 SCV002763579 uncertain significance Fibromatosis, gingival, 1 criteria provided, single submitter clinical testing
GeneDx RCV004762245 SCV005369334 uncertain significance not provided 2023-07-24 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); Missense variants in this gene are often considered pathogenic (HGMD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 29493581)

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