ClinVar Miner

Submissions for variant NM_000435.3(NOTCH3):c.2149C>T (p.Arg717Cys) (rs144163298)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000991701 SCV001143369 uncertain significance not provided 2018-12-05 criteria provided, single submitter clinical testing
Ambry Genetics RCV001266935 SCV001445116 uncertain significance Inborn genetic diseases 2018-06-19 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000991701 SCV001501696 likely pathogenic not provided 2020-10-01 criteria provided, single submitter clinical testing
Invitae RCV000991701 SCV001563444 uncertain significance not provided 2020-10-20 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 717 of the NOTCH3 protein (p.Arg717Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs144163298, ExAC 0.005%). This variant has been observed in individual(s) with cerebral arteriopathy with subcortical infarcts and leukoencephalopathy (PMID: 26308724). ClinVar contains an entry for this variant (Variation ID: 804628). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt NOTCH3 protein function. 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.
Myllykangas group,University of Helsinki RCV001263185 SCV001250697 uncertain significance Vascular dementia 2020-04-01 no assertion criteria provided research

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