ClinVar Miner

Submissions for variant NM_000435.3(NOTCH3):c.2182C>T (p.Arg728Cys)

gnomAD frequency: 0.00001  dbSNP: rs1057519101
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Center for Human Genetics Tuebingen RCV000416179 SCV000493174 likely pathogenic not provided 2023-03-01 criteria provided, single submitter clinical testing NOTCH3: PM1:Strong, PM2, PS4:Moderate, PP2, PP4, BP4
GeneDx RCV000416179 SCV002499947 uncertain significance not provided 2022-03-31 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 9388399, 27781952, 27455010, 19174371, 21616505, 11102981, 25344745, 31589614, 33478738, 24844136, 23639391)
Athena Diagnostics Inc RCV000416179 SCV004229490 pathogenic not provided 2022-10-06 criteria provided, single submitter clinical testing The frequency of this variant in the general population is consistent with pathogenicity (http://gnomad.broadinstitute.org). This variant has been identified in at least one individual with clinical features of CADASIL. This variant alters a critical location within the protein, and is expected to severely affect function and cause disease. Greater than 90% of NOTCH3 pathogenic variants associated with CADASIL involve the gain or loss of a cysteine residue within the epidermal growth factor (EGF)-like repeat domain (PMID: 32457593, 20301673).
Gharavi Laboratory, Columbia University RCV000416179 SCV000920662 uncertain significance not provided 2018-09-16 no assertion criteria provided research
Genome Diagnostics Laboratory, Amsterdam University Medical Center RCV000416179 SCV002035213 pathogenic not provided no assertion criteria provided clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) RCV000416179 SCV002036413 likely pathogenic not provided no assertion criteria provided clinical testing

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