ClinVar Miner

Submissions for variant NM_017617.5(NOTCH1):c.2576C>T (p.Thr859Met)

gnomAD frequency: 0.00004  dbSNP: rs199505287
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002315141 SCV000739513 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2023-03-12 criteria provided, single submitter clinical testing The p.T859M variant (also known as c.2576C>T), located in coding exon 16 of the NOTCH1 gene, results from a C to T substitution at nucleotide position 2576. The threonine at codon 859 is replaced by methionine, an amino acid with similar properties. This amino acid position is poorly 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 RCV000655238 SCV000777168 benign Adams-Oliver syndrome 5 2024-01-16 criteria provided, single submitter clinical testing
GeneDx RCV001558346 SCV001780272 uncertain significance not provided 2023-05-04 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function
Genome-Nilou Lab RCV000655238 SCV002553543 uncertain significance Adams-Oliver syndrome 5 2022-03-15 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV002270922 SCV002553544 uncertain significance Aortic valve disease 1 2022-03-15 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002483735 SCV002788309 uncertain significance Aortic valve disease 1; Adams-Oliver syndrome 5 2021-10-08 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004544814 SCV004790710 uncertain significance NOTCH1-related disorder 2023-11-30 no assertion criteria provided clinical testing The NOTCH1 c.2576C>T variant is predicted to result in the amino acid substitution p.Thr859Met. To our knowledge, this variant has not been reported in the literature in individuals with NOTCH1-related disorders. This variant is reported in 0.0063% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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