ClinVar Miner

Submissions for variant NM_006939.4(SOS2):c.1612G>A (p.Ala538Thr)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002400924 SCV002707940 uncertain significance Cardiovascular phenotype 2021-11-28 criteria provided, single submitter clinical testing The p.A538T variant (also known as c.1612G>A), located in coding exon 10 of the SOS2 gene, results from a G to A substitution at nucleotide position 1612. The alanine at codon 538 is replaced by threonine, an amino acid with similar 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.
CeGaT Center for Human Genetics Tuebingen RCV003395476 SCV004134086 uncertain significance not provided 2023-10-01 criteria provided, single submitter clinical testing SOS2: PM2
Labcorp Genetics (formerly Invitae), Labcorp RCV003591955 SCV004265442 uncertain significance Noonan syndrome 9 2024-06-03 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 538 of the SOS2 protein (p.Ala538Thr). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SOS2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1776424). 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 SOS2 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.

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