ClinVar Miner

Submissions for variant NM_017617.5(NOTCH1):c.7279G>A (p.Gly2427Ser) (rs370722609)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000228959 SCV000290308 uncertain significance Adams-Oliver syndrome 5 2016-01-25 criteria provided, single submitter clinical testing This sequence change replaces glycine with serine at codon 2427 of the NOTCH1 protein (p.Gly2427Ser). The glycine residue is moderately conserved and there is a small physicochemical difference between glycine and serine. This variant is present in population databases (rs370722609, ExAC 0.01%) but has not been reported in the literature in individuals with a NOTCH1-related disease. The serine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. In addition, 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. In summary, this is a rare missense change with uncertain impact on protein function. There is no indication that this variant causes disease, but the evidence is insufficient at this time to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Blueprint Genetics RCV000788485 SCV000927621 uncertain significance not provided 2018-04-09 criteria provided, single submitter clinical testing

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