ClinVar Miner

Submissions for variant NM_005633.4(SOS1):c.3960C>G (p.His1320Gln)

dbSNP: rs1553349464
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000521073 SCV000621418 uncertain significance not provided 2017-10-04 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the SOS1 gene. The H1320Q variant has not been publishedas pathogenic or been reported as benign to our knowledge. This variant is not observed in large population cohorts(Lek et al., 2016). The H1320Q variant is a semi-conservative amino acid substitution, which may impact secondaryprotein structure as these residues differ in some properties. This substitution occurs at a position that is conservedacross species, and in silico analysis suggests that this variant is probably damaging to the protein structure/function.However, no missense variants in nearby residues have been reported in the Human Gene Mutation Database inassociation with SOS1-related disorders (Stenson et al., 2014).
Labcorp Genetics (formerly Invitae), Labcorp RCV001858033 SCV002211829 uncertain significance RASopathy 2021-07-26 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 452599). This variant has not been reported in the literature in individuals affected with SOS1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces histidine with glutamine at codon 1320 of the SOS1 protein (p.His1320Gln). The histidine residue is moderately conserved and there is a small physicochemical difference between histidine and glutamine.
Genome-Nilou Lab RCV002467861 SCV002763181 uncertain significance Noonan syndrome 4 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV002467860 SCV002763182 uncertain significance Fibromatosis, gingival, 1 criteria provided, single submitter clinical testing

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