ClinVar Miner

Submissions for variant NM_000435.3(NOTCH3):c.3182G>A (p.Cys1061Tyr) (rs1064794216)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000485488 SCV000568237 likely pathogenic not provided 2018-03-22 criteria provided, single submitter clinical testing The C1061Y variant in the NOTCH3 gene has been reported previously in association with CADASIL (Zhang et al., 2012). The C1061Y variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The C1061Y variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. The C1061Y variant is a strong candidate for a pathogenic variant.
Athena Diagnostics Inc RCV000485488 SCV000614278 pathogenic not provided 2019-05-14 criteria provided, single submitter clinical testing The variant disrupts a cysteine residue in an EGF-like repeat domain, which are important for the structure of this protein. Therefore it is expected to severely affect the function of the protein. Found in at least one symptomatic patient, and not found in general population data. Reported in a patient with CADASIL.

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