Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
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. |
| Labcorp Genetics |
RCV000483202 | SCV000932998 | pathogenic | not provided | 2024-01-05 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Lys834*) in the ELP1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ELP1 are known to be pathogenic (PMID: 18303054, 24173031). This variant is present in population databases (rs767527819, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with ELP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 423215). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
| Fulgent Genetics, |
RCV000793636 | SCV001752800 | pathogenic | Familial dysautonomia | 2021-06-30 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV004023187 | SCV003895125 | pathogenic | not specified | 2023-02-10 | criteria provided, single submitter | clinical testing | The c.2499dupT (p.K834*) alteration, located in exon 23 (coding exon 22) of the IKBKAP gene, consists of a duplication of T at position 2499. This changes the amino acid from a lysine (K) to a stop codon at amino acid position 834. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. Based on data from gnomAD, the TT allele has an overall frequency of 0.002% (5/251338) total alleles studied. The highest observed frequency was 0.004% (5/113630) of European (non-Finnish) alleles. Based on the available evidence, this alteration is classified as pathogenic. |
| Counsyl | RCV000793636 | SCV001132233 | likely pathogenic | Familial dysautonomia | 2017-05-15 | no assertion criteria provided | clinical testing |