ClinVar Miner

Submissions for variant NM_005633.4(SOS1):c.3748C>T (p.Pro1250Ser)

dbSNP: rs1668548624
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001928214 SCV002178893 uncertain significance RASopathy 2023-02-17 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1250 of the SOS1 protein (p.Pro1250Ser). This variant is not present in population databases (gnomAD no frequency). 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: 1413657). 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 not expected to disrupt SOS1 protein function. 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.
Ambry Genetics RCV002344023 SCV002621249 uncertain significance Cardiovascular phenotype 2020-09-18 criteria provided, single submitter clinical testing The p.P1250S variant (also known as c.3748C>T), located in coding exon 23 of the SOS1 gene, results from a C to T substitution at nucleotide position 3748. This alteration was identified in a non-cancer control cohort; however, details were limited (Pritchard AL et al. PLoS ONE, 2018 Apr;13:e0194098). The proline at codon 1250 is replaced by serine, an amino acid with similar properties. This amino acid position is highly 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.
Genome-Nilou Lab RCV002468352 SCV002763540 uncertain significance Noonan syndrome 4 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV002468351 SCV002763541 uncertain significance Fibromatosis, gingival, 1 criteria provided, single submitter clinical testing

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