ClinVar Miner

Submissions for variant NM_005633.3(SOS1):c.1010A>G (p.Tyr337Cys) (rs724160007)

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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 RCV000154291 SCV000203950 uncertain significance not specified 2014-08-14 criteria provided, single submitter clinical testing The Tyr337Cys variant in SOS1 has been reported in 1 individual with clinical fe atures of Noonan syndrome (Roberts 2007), but has also been reported to be prese nt in 2 unaffected individuals from one family (Personal Communication). This va riant was absent from large population studies. Studies have shown that the Tyr3 37Cys variant may impact protein function by increasing its activity though thes e results are inconclusive and these in vitro assays may not accurately represen t biological function (Smith 2013). Due to the conflicting data about this varia nt, the clinical significance of the Tyr337Cys variant is uncertain.
Invitae RCV000149848 SCV001395229 uncertain significance Rasopathy 2019-09-27 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with cysteine at codon 337 of the SOS1 protein (p.Tyr337Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is present in population databases (rs724160007, ExAC 0.03%). This variant has been observed in an individual affected with Noonan syndrome (PMID: 17143285). ClinVar contains an entry for this variant (Variation ID: 162463). This variant has been reported to have conflicting or insufficient data to determine the effect on SOS1 protein function (PMID: 17143285, 23487764). 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.
Baylor Genetics RCV000149848 SCV000196693 uncertain significance Rasopathy no assertion criteria provided clinical testing Variant classified using ACMG guidelines

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