Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Baylor Genetics | RCV000679951 | SCV000807385 | uncertain significance | Megaconial type congenital muscular dystrophy | 2017-09-01 | criteria provided, single submitter | clinical testing | Likely pathogenicity based on finding it once in our laboratory in a homozygous state in a 13-year-old male with developmental delay, hypotonia, myopathy, speech delay, memory problems. This change, which occurred at the +3 position at the exon/intron junction, might affect mRNA splicing based on in silico predictions. |
| Labcorp Genetics |
RCV000679951 | SCV001381006 | pathogenic | Megaconial type congenital muscular dystrophy | 2021-02-09 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant results in alternate splicing of exon 9, which introduces a new termination codon (PMID: 25740612). However the mRNA is not expected to undergo nonsense-mediated decay. This variant has been observed in individual(s) with congenital muscular dystrophy (PMID: 25740612, 25326635, Invitae). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 560978). This variant is present in population databases (rs751176079, ExAC 0.02%). This sequence change falls in intron 9 of the CHKB gene. It does not directly change the encoded amino acid sequence of the CHKB protein. RNA analysis indicates that this variant induces altered splicing and likely disrupts the C-terminus of the protein. |