ClinVar Miner

Submissions for variant NM_003640.5(ELP1):c.2499dup (p.Lys834Ter) (rs767527819)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000483202 SCV000572879 likely pathogenic not provided 2017-01-31 criteria provided, single submitter clinical testing A novel c.2499dupT variant that is likely pathogenic has been identified in the IKBKAP gene. The c.2499dupT variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The c.2499dupT variant causes a frameshift starting with codon Lysine 834 and changes this amino acid to a premature Stop codon, denoted p.Lys834Ter. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Furthermore, the c.2499dupT variant is not observed with any significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.
Invitae RCV000793636 SCV000932998 pathogenic Familial dysautonomia 2018-08-27 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Lys834*) in the IKBKAP gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs767527819, ExAC 0.003%). This variant has not been reported in the literature in individuals with IKBKAP-related disease. ClinVar contains an entry for this variant (Variation ID: 423215). Loss-of-function variants in IKBKAP are known to be pathogenic (PMID: 18303054, 24173031). For these reasons, this variant has been classified as Pathogenic.

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