ClinVar Miner

Submissions for variant NM_017617.5(NOTCH1):c.4014G>A (p.Ala1338=) (rs377217445)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000620549 SCV000739358 uncertain significance Cardiovascular phenotype 2016-06-22 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000727323 SCV000707557 uncertain significance not provided 2017-04-18 criteria provided, single submitter clinical testing
GeneDx RCV000727323 SCV000617083 uncertain significance not provided 2017-07-13 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the NOTCH1 gene. The c.4014 G>A variant has been reported in one ostensibly healthy individual of mixed African and European ancestry who underwent whole genome sequencing (Bodian et al., 2014), although a follow-up cardiac evaluation was not reported. It has also been observed in 10/3078 (0.325%) alleles from individuals of African ancestry in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). While c.4014 G>A (A1338=) does not alter the predicted amino acid sequence, in silico splice prediction algorithms predict this variant may destroy the natural splice donor site of intron 24 and lead to abnormal gene splicing. However, in the absence of functional mRNA studies, the physiological consequence of this variant cannot be precisely determined. Lastly, c.4014 G>A is located at the last nucleotide position of exon 12 and this nucleotide is not conserved across species.
ITMI RCV000121681 SCV000085879 not provided not specified 2013-09-19 no assertion provided reference population
Invitae RCV000535642 SCV000659436 likely benign Adams-Oliver syndrome 5 2017-04-17 criteria provided, single submitter clinical testing

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