ClinVar Miner

Submissions for variant NM_005633.3(SOS1):c.2156G>C (p.Gly719Ala) (rs200794965)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen RASopathy Variant Curation Expert Panel RCV000231034 SCV000616514 likely benign Rasopathy 2017-04-18 reviewed by expert panel curation The filtering allele frequency of the c.2156G>C (p.Gly719Ala) variant in the SOS1 gene is 0.0414% (37/66598) of European chromosomes by the Exome Aggregation Consortium, which is a high enough frequency to be classified as likely benign based on thresholds defined by the ClinGen RASopathy Expert Panel (BS1; PMID:29493581)
GeneDx RCV000159125 SCV000209069 likely benign not provided 2019-01-23 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV000231034 SCV000288961 uncertain significance Rasopathy 2016-01-02 criteria provided, single submitter clinical testing This sequence change replaces glycine with alanine at codon 719 of the SOS1 protein (p.Gly719Ala). The glycine residue is moderately conserved and there is a small physicochemical difference between glycine and alanine. This variant is present in population databases (rs200794965, ExAC 0.06%) but has not been reported in the literature in individuals with a SOS1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. In summary, this is a rare missense change that is not predicted to affect protein function or cause disease. However, the evidence is insufficient at this time to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

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