Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001859529 | SCV002240201 | pathogenic | Progressive myoclonic epilepsy | 2021-11-05 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 268146). This premature translational stop signal has been observed in individuals with progressive myoclonic epilepsy (PMID: 24485911, 24620919). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Arg424*) in the SCARB2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SCARB2 are known to be pathogenic (PMID: 19847901). For these reasons, this variant has been classified as Pathogenic. |
Ambry Genetics | RCV002374447 | SCV002683728 | pathogenic | Inborn genetic diseases | 2018-09-10 | criteria provided, single submitter | clinical testing | The p.R424* pathogenic mutation (also known as c.1270C>T), located in coding exon 11 of the SCARB2 gene, results from a C to T substitution at nucleotide position 1270. This changes the amino acid from an arginine to a stop codon within coding exon 11. This variant was detected in the homozygous state in an individual with unsteady gait, myoclonus, tremors, seizures; both parents were confirmed carriers (Zeigler M et al. J. Neurol. Sci., 2014 Apr;339:210-3). In another family, this mutation was detected in the homozygous state in two similarly affected siblings with gait disorder, and tremor; one sibling had seizures and a paternally inherited variant in KCNQ2, which was absent from the second sibling (He M et al. Clin. Genet., 2014 Dec;86:598-600). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
Fulgent Genetics, |
RCV000258865 | SCV002787678 | pathogenic | Action myoclonus-renal failure syndrome | 2022-01-25 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000258865 | SCV000328643 | not provided | Action myoclonus-renal failure syndrome | no assertion provided | literature only |