ClinVar Miner

Submissions for variant NM_005633.4(SOS1):c.199G>A (p.Ala67Thr)

gnomAD frequency: 0.00001  dbSNP: rs730881053
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000159186 SCV000209132 uncertain significance not provided 2014-10-09 criteria provided, single submitter clinical testing The A67T variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The A67T variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The A67T variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is moderately conserved across species. However, in silico analysis predicts this variant likely does not alter the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in CARDIOMYOPATHY panel(s).
Labcorp Genetics (formerly Invitae), Labcorp RCV001309736 SCV001499244 uncertain significance RASopathy 2020-07-31 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 67 of the SOS1 protein (p.Ala67Thr). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs730881053, ExAC 0.01%). This variant has not been reported in the literature in individuals with SOS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 181558). 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 and their clinical significance is uncertain. 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.
Genome-Nilou Lab RCV002467637 SCV002763605 uncertain significance Noonan syndrome 4 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV002467636 SCV002763606 uncertain significance Fibromatosis, gingival, 1 criteria provided, single submitter clinical testing

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