ClinVar Miner

Submissions for variant NM_017617.5(NOTCH1):c.2207+5G>A

gnomAD frequency: 0.00001  dbSNP: rs1214619547
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000655266 SCV000777196 uncertain significance Adams-Oliver syndrome 5 2022-08-16 criteria provided, single submitter clinical testing 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. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 544190). This variant has not been reported in the literature in individuals affected with NOTCH1-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change falls in intron 13 of the NOTCH1 gene. It does not directly change the encoded amino acid sequence of the NOTCH1 protein. It affects a nucleotide within the consensus splice site.
GeneDx RCV001771915 SCV001992519 uncertain significance not provided 2019-04-26 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 544190; Landrum et al., 2016); Not observed in large population cohorts (Lek et al., 2016); Splice site variant expected to result in aberrant splicing, though splice outcome is unknown; Other splicing variants in NOTCH1 have been reported in HGMD in association with NOTCH1-related disorders, although the majority of reported NOTCH1 variants are missense variants (Stenson et al., 2014)
Genome-Nilou Lab RCV000655266 SCV002553574 uncertain significance Adams-Oliver syndrome 5 2022-03-15 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV002270944 SCV002553575 uncertain significance Aortic valve disease 1 2022-03-15 criteria provided, single submitter clinical testing

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