ClinVar Miner

Submissions for variant NM_005633.4(SOS1):c.1220T>A (p.Phe407Tyr)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002368995 SCV002659012 uncertain significance Cardiovascular phenotype 2019-09-09 criteria provided, single submitter clinical testing The p.F407Y variant (also known as c.1220T>A), located in coding exon 10 of the SOS1 gene, results from a T to A substitution at nucleotide position 1220. The phenylalanine at codon 407 is replaced by tyrosine, an amino acid with highly similar properties. This amino acid position is well 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV003539429 SCV004265948 uncertain significance RASopathy 2024-01-22 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine, which is neutral and non-polar, with tyrosine, which is neutral and polar, at codon 407 of the SOS1 protein (p.Phe407Tyr). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with SOS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1753021). 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 with a positive predictive value of 80%. 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.

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