ClinVar Miner

Submissions for variant NM_006939.4(SOS2):c.575G>C (p.Ser192Thr)

gnomAD frequency: 0.00001  dbSNP: rs1886005182
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV001797010 SCV002038524 uncertain significance Noonan syndrome 9 2021-05-20 criteria provided, single submitter clinical testing The SOS2 c.575G>C (p.Ser192Thr) variant is a missense variant. A literature search was performed for the gene, cDNA change, and amino acid change. No publications were found based on this search. This variant is reported at a frequency of 0.000029 in the European (non-Finnish) population of version v3.1.1 of the Genome Aggregation Database, though this is based on two alleles in a region of good sequence coverage so the variant is presumed to be rare. Based on the limited evidence, the p.Ser192Thr variant is classified as a variant of uncertain significance for Noonan syndrome.
Labcorp Genetics (formerly Invitae), Labcorp RCV001797010 SCV004551774 uncertain significance Noonan syndrome 9 2023-10-20 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with threonine, which is neutral and polar, at codon 192 of the SOS2 protein (p.Ser192Thr). 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: 1328526). 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 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.
Ambry Genetics RCV004671442 SCV005170336 uncertain significance Cardiovascular phenotype 2024-05-06 criteria provided, single submitter clinical testing The c.575G>C (p.S192T) alteration is located in exon 5 (coding exon 5) of the SOS2 gene. This alteration results from a G to C substitution at nucleotide position 575, causing the serine (S) at amino acid position 192 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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