ClinVar Miner

Submissions for variant NM_006939.4(SOS2):c.2030A>G (p.Lys677Arg)

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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 RCV004353091 SCV004081013 uncertain significance Cardiovascular phenotype 2023-08-08 criteria provided, single submitter clinical testing The c.2030A>G (p.K677R) alteration is located in exon 12 (coding exon 12) of the SOS2 gene. This alteration results from a A to G substitution at nucleotide position 2030, causing the lysine (K) at amino acid position 677 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV005104160 SCV005742843 uncertain significance Noonan syndrome 9 2024-03-05 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 677 of the SOS2 protein (p.Lys677Arg). 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: 2617413). 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 with a negative 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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