Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Foundation for Research in Genetics and Endocrinology, |
RCV001420189 | SCV001622392 | pathogenic | Metachromatic leukodystrophy | 2021-04-20 | criteria provided, single submitter | clinical testing | A homozygous single base pair deletion in exon 4 of the ARSA gene that results in a frameshift and premature truncation of the protein 5 amino acids downstream to codon 195 was detected. The variant c.582del (p.Trp195Glyfs*5) has not been reported in 1000 genomes and gnomAD databases. The in silico prediction of the variant is damaging by MutationTaster2. The reference region is conserved across species. In summary, the variant meets our criteria to be classified as pathogenic. |
Labcorp Genetics |
RCV001420189 | SCV003484208 | pathogenic | Metachromatic leukodystrophy | 2023-11-28 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Trp195Glyfs*5) in the ARSA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ARSA are known to be pathogenic (PMID: 8962139, 10477432). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with metachromatic leukodystrophy (PMID: 30674982). This variant is also known as c.576delC. ClinVar contains an entry for this variant (Variation ID: 1098313). For these reasons, this variant has been classified as Pathogenic. |