ClinVar Miner

Submissions for variant NM_006939.4(SOS2):c.2667G>T (p.Glu889Asp)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002574502 SCV003487257 uncertain significance Noonan syndrome 9 2024-10-04 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 889 of the SOS2 protein (p.Glu889Asp). This variant also falls at the last nucleotide of exon 16, which is part of the consensus splice site for this exon. 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: 2173038). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt SOS2 protein function with a negative predictive value of 95%. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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 RCV004073359 SCV003588243 uncertain significance Cardiovascular phenotype 2021-12-03 criteria provided, single submitter clinical testing The c.2667G>T (p.E889D) alteration is located in exon 16 (coding exon 16) of the SOS2 gene. This alteration results from a G to T substitution at nucleotide position 2667, causing the glutamic acid (E) at amino acid position 889 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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