ClinVar Miner

Submissions for variant NM_005633.4(SOS1):c.3971C>G (p.Pro1324Arg)

dbSNP: rs727503434
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000151916 SCV000200432 uncertain significance not specified 2014-07-07 criteria provided, single submitter clinical testing The Pro1324Arg variant in SOS1 has not been previously reported in individuals w ith clinical features of a Noonan spectrum disorder and was absent from large po pulation studies. Computational prediction tools and evolutionary conservation a nalysis do not provide strong support for or against an impact to the protein. I n summary, additional information is needed to determine the clinical significan ce of this variant.
Labcorp Genetics (formerly Invitae), Labcorp RCV001343471 SCV001537455 uncertain significance RASopathy 2023-11-21 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 1324 of the SOS1 protein (p.Pro1324Arg). This variant is present in population databases (rs727503434, gnomAD 0.006%). 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: 165276). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on 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 RCV002371996 SCV002625077 uncertain significance Cardiovascular phenotype 2021-03-08 criteria provided, single submitter clinical testing The p.P1324R variant (also known as c.3971C>G), located in coding exon 23 of the SOS1 gene, results from a C to G substitution at nucleotide position 3971. The proline at codon 1324 is replaced by arginine, an amino acid with dissimilar 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 RCV002467593 SCV002763179 uncertain significance Noonan syndrome 4 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV002467592 SCV002763180 uncertain significance Fibromatosis, gingival, 1 criteria provided, single submitter clinical testing

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