ClinVar Miner

Submissions for variant NM_005506.4(SCARB2):c.1270C>T (p.Arg424Ter)

gnomAD frequency: 0.00001  dbSNP: rs886041078
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Total submissions: 4
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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, Fulgent Genetics RCV000258865 SCV002787678 pathogenic Action myoclonus-renal failure syndrome 2022-01-25 criteria provided, single submitter clinical testing
GeneReviews RCV000258865 SCV000328643 not provided Action myoclonus-renal failure syndrome no assertion provided literature only

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