ClinVar Miner

Submissions for variant NM_017617.5(NOTCH1):c.4031C>T (p.Thr1344Met) (rs201215245)

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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 RCV000620997 SCV000739413 uncertain significance Cardiovascular phenotype 2016-06-07 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000770630 SCV000902081 uncertain significance Thoracic aortic aneurysm and aortic dissection 2017-10-10 criteria provided, single submitter clinical testing
GeneDx RCV000523711 SCV000618225 uncertain significance not provided 2017-12-08 criteria provided, single submitter clinical testing The T1344M variant in the NOTCH1 gene has been reported as a variant of uncertain significance in two individuals from a cohort of patients with nonsyndromic left-sided congenital heart disease (Kerstjens-Frederikse et al., 2016). The first patient presented with bicuspid aortic valve and no parental studies were performed. The second patient presented with hypoplastic left heart syndrome and T1344M was found to be inherited from a mother with a normal cardiac ultrasound (Kerstjens-Frederikse et al., 2016). The T1344M variant is observed in 113/244232 (0.05%) alleles in large population cohorts (Lek et al., 2016). The T1344M variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. We interpret T1344M as a variant of uncertain significance.
Invitae RCV000560526 SCV000659438 likely benign Adams-Oliver syndrome 5 2017-12-18 criteria provided, single submitter clinical testing

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