Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Mayo Clinic Laboratories, |
RCV001507724 | SCV001713452 | likely pathogenic | not provided | 2020-07-17 | criteria provided, single submitter | clinical testing | PVS1, PM2 |
| Instituto de Biomedicina de Sevilla, |
RCV001647301 | SCV001860342 | pathogenic | Spinal muscular atrophy-progressive myoclonic epilepsy syndrome | criteria provided, single submitter | research | By exome sequencing, two compund heterozygous variants in ASAH1 were identified. One of them, NM_177924.4:c.456ª>C p.(Lys152Asn) in exón 6, had been reported previously in a paciente with SMA-EMP phenotype as a compound heterozygous with the non-sense p.Gly284* by Dyment et al 2014. This variant is not present in databases of normal controls (Genome aggregation database). It lies 2 nucleotides away from the intron-exon boundary, and it was confirmed to cause skipping of exón 6 in skin fibroblast. The second variant detected is the novel NM_177924.4:c3G>T in exón 1. It is absent from population databases, and causes loss of the initiation ATG codon, which is likely to result in loss of mRNA transcription and therefore protein function. Sequencing of both parents´DNA confirmed each of them is heterozygous for one of the variants, confirming the variants are in trans in the patient. We observed absence of ASAH1 protein in muscle by western blot. Both variants are classified as pathogenic (class 5) applying ACGM rules. | |
| Fulgent Genetics, |
RCV002506589 | SCV002808709 | likely pathogenic | Spinal muscular atrophy-progressive myoclonic epilepsy syndrome; Farber lipogranulomatosis | 2022-03-10 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001507724 | SCV005822242 | pathogenic | not provided | 2024-12-19 | criteria provided, single submitter | clinical testing | This sequence change affects the initiator methionine of the ASAH1 mRNA. The next in-frame methionine is located at codon 66. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ASAH1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1163018). This variant disrupts a region of the ASAH1 protein in which other variant(s) (p.Thr42Met) have been determined to be pathogenic (PMID: 22703880, 25578555, 25847462, 27723502). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |