ClinVar Miner

Submissions for variant NM_005633.3(SOS1):c.643T>C (p.Tyr215His) (rs730881039)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen RASopathy Variant Curation Expert Panel RCV000704276 SCV001192870 uncertain significance Rasopathy 2019-09-24 reviewed by expert panel curation The c.643T>C (p.Tyr215His) variant in the SOS1 gene is present in 0.014% (5/35434) Latino alleles in gnomAD (BS1 not met). This variant was observed in 9 healthy adult individuals who did not have clinical features of a RASopathy (BS2; SCV000209098.13). In summary, the clinical significance of the p.Tyr215His variant is uncertain. RASopathy-specific ACMG/AMP criteria applied (PMID:29493581): BS2.
GeneDx RCV000159154 SCV000209098 likely benign not provided 2018-02-14 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 RCV000704276 SCV000833218 uncertain significance Rasopathy 2018-01-31 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with histidine at codon 215 of the SOS1 protein (p.Tyr215His). The tyrosine residue is moderately conserved and there is a moderate physicochemical difference between tyrosine and histidine. This variant is present in population databases (rs730881039, ExAC 0.02%). This variant has not been reported in the literature in individuals with SOS1-related disease. ClinVar contains an entry for this variant (Variation ID: 181547). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.
Illumina Clinical Services Laboratory,Illumina RCV001141421 SCV001301765 uncertain significance Noonan syndrome 4 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina RCV001141422 SCV001301766 uncertain significance Gingival fibromatosis 1 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

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