ClinVar Miner

Submissions for variant NM_017617.5(NOTCH1):c.2558_2560del (p.Phe853del) (rs779164170)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000522624 SCV000620397 uncertain significance not provided 2018-10-09 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the NOTCH1 gene. The c.2558_2560delTCT variant has not been published as pathogenic or been reported as benign to our knowledge. The c.2558_2560delTCT variant is observed in 4/65012 (0.006%) alleles from individuals of Non-Finnish European background in the Exome Aggregation Consortium (ExAC) dataset (Lek et al., 2016). The c.2558_2560delTCT variant results in an in-frame deletion of a phenylalanine (F) residue at codon 853, denoted p.F853del, and does not result in a shift in reading frame or a premature stop codon. Additionally, no in-frame deletions in the NOTCH1 gene have been reported in the Human Gene Mutation Database in association with disease (Stenson et al., 2014).
Invitae RCV000803586 SCV000943465 uncertain significance Adams-Oliver syndrome 5 2019-12-18 criteria provided, single submitter clinical testing This variant, c.2558_2560delTCT, results in the deletion of 1 amino acid(s) of the NOTCH1 protein (p.Phe853del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs779164170, ExAC 0.006%). This variant has not been reported in the literature in individuals with NOTCH1-related disease. ClinVar contains an entry for this variant (Variation ID: 451668). Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the deleted amino acid is currently unknown. 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.

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