ClinVar Miner

Submissions for variant NM_017617.5(NOTCH1):c.3879C>T (p.Cys1293=)

gnomAD frequency: 0.00001  dbSNP: rs777242726
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001324290 SCV001515239 uncertain significance Adams-Oliver syndrome 5 2020-08-29 criteria provided, single submitter clinical testing This sequence change affects codon 1293 of the NOTCH1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the NOTCH1 protein. 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with NOTCH1-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database.
GeneDx RCV003442847 SCV004169740 uncertain significance not provided 2023-11-06 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function

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