Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000623181 | SCV000740751 | likely pathogenic | Inborn genetic diseases | 2014-10-23 | criteria provided, single submitter | clinical testing | The c.145-2A>G intronic alteration consists of a A to G substitution 2 nucleotides before coding exon 2 in the KCTD7 gene. The alteration is not observed in healthy cohorts:_x000D_ Based on data from the NHLBI Exome Sequencing Project (ESP), the KCTD7 c.145-2A>G alteration was not observed among 6,503 individuals tested. Allele frequency data for this nucleotide position are not currently available from the 1000 Genomes Project and the alteration is not currently listed in the Database of Single Nucleotide Polymorphisms (dbSNP)._x000D_ Though some variants may appear to be rare due to database-specific ethnic underrepresentation, rare missense alleles commonly exhibit a deleterious effect on protein function (Kryukov, 2007; Tennessen, 2012). IF USED, PULL THESE INTO REFERENCES:_x000D_ Kryukov GV, et al. (2007) Am J Hum Genet 80:727-739. Tennessen JA, et al. (2012) Science 337(64):64-69. The alteration is predicted to affect splicing by in silico models:_x000D_ Based on BDGP and ESEfinder splice site in silico tools, this alteration is predicted to abolish the native splice acceptor site; however, direct evidence is unavailable. Based on the available evidence, this alteration is classified as likely pathogenic. |
| Labcorp Genetics |
RCV001042252 | SCV001205925 | likely pathogenic | Progressive myoclonic epilepsy type 3 | 2024-06-03 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 1 of the KCTD7 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in KCTD7 are known to be pathogenic (PMID: 22693283). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with progressive myoclonus epilepsy (PMID: 26795593). ClinVar contains an entry for this variant (Variation ID: 520584). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| New York Genome Center | RCV001042252 | SCV001815754 | likely pathogenic | Progressive myoclonic epilepsy type 3 | 2020-08-14 | criteria provided, single submitter | clinical testing | |
| Department of Pathology and Laboratory Medicine, |
RCV005357820 | SCV005918636 | likely pathogenic | Progressive myoclonic epilepsy | 2021-12-02 | criteria provided, single submitter | research |