ClinVar Miner

Submissions for variant NM_017617.5(NOTCH1):c.2352C>T (p.Ser784=)

gnomAD frequency: 0.00009  dbSNP: rs774701000
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000547527 SCV000659400 uncertain significance Adams-Oliver syndrome 5 2024-01-22 criteria provided, single submitter clinical testing This sequence change affects codon 784 of the NOTCH1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the NOTCH1 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs774701000, gnomAD 0.02%). This variant has been observed in individual(s) with bicuspid aortic valve-associated thoracic aortic aneurysm (PMID: 28659821). ClinVar contains an entry for this variant (Variation ID: 477897). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. 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.
GeneDx RCV001697385 SCV000721256 likely benign not provided 2019-07-05 criteria provided, single submitter clinical testing
Ambry Genetics RCV002448806 SCV002733120 likely benign Familial thoracic aortic aneurysm and aortic dissection 2017-10-26 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001697385 SCV004563272 likely benign not provided 2023-02-21 criteria provided, single submitter clinical testing

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