ClinVar Miner

Submissions for variant NM_017617.5(NOTCH1):c.6851C>T (p.Thr2284Ile)

dbSNP: rs1341934554
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002315143 SCV000739515 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2017-12-12 criteria provided, single submitter clinical testing The p.T2284I variant (also known as c.6851C>T), located in coding exon 34 of the NOTCH1 gene, results from a C to T substitution at nucleotide position 6851. The threonine at codon 2284 is replaced by isoleucine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV001222420 SCV001394518 uncertain significance Adams-Oliver syndrome 5 2022-09-13 criteria provided, single submitter clinical testing This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with NOTCH1-related conditions. ClinVar contains an entry for this variant (Variation ID: 520099). 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 not expected to disrupt NOTCH1 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. This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 2284 of the NOTCH1 protein (p.Thr2284Ile).
Genome-Nilou Lab RCV001222420 SCV002553274 uncertain significance Adams-Oliver syndrome 5 2022-03-15 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV002270924 SCV002553275 uncertain significance Aortic valve disease 1 2022-03-15 criteria provided, single submitter clinical testing

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