ClinVar Miner

Submissions for variant NM_005633.3(SOS1):c.512T>G (p.Val171Gly) (rs397517174)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000038563 SCV000062241 uncertain significance not specified 2014-09-25 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Pathogenic. The Val171Gly v ariant in SOS1 has been previously identified in one individual with clinical fe atures of Noonan syndrome (LMM unpublished data). It was absent from large popul ation studies. In addition, another variant (Val171Ala) at the same codon was id entified as a de novo variant in one proband with clinical features of Noonan sy ndrome (LMM unpublished data) suggesting that changes at this position may not b e tolerated. Computational prediction tools and conservation analysis do not pro vide strong support for or against an impact to the protein. In summary, while t he available data on the Val171Gly variant is suspicious to be pathogenic, the c linical significance of this variant is uncertain.
Invitae RCV000466303 SCV000553263 uncertain significance Rasopathy 2016-08-22 criteria provided, single submitter clinical testing This sequence change replaces valine with glycine at codon 171 of the SOS1 protein (p.Val171Gly). The valine residue is highly conserved and there is a moderate physicochemical difference between valine and glycine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a SOS1-related disease. ClinVar contains an entry for this variant (Variation ID: 40654). 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000624181 SCV000742607 likely pathogenic Inborn genetic diseases 2017-05-26 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: LIKELY POSITIVE: Relevant Alteration(s) Detected

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