Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000760414 | SCV000890291 | pathogenic | not provided | 2018-10-25 | criteria provided, single submitter | clinical testing | The K437X variant in the ALDH3A2 gene has been reported previously in the homozygous state in two unrelated Honduran individuals with Sjogren-Larsson syndrome with varying disease severity (Davis et al., 2013). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The K437X variant is not observed in large population cohorts (Lek et al., 2016). We interpret K437X as a pathogenic variant. |
Invitae | RCV000760414 | SCV003441756 | pathogenic | not provided | 2023-06-25 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 619024). This premature translational stop signal has been observed in individual(s) with Sjogren-Larsson syndrome (PMID: 23034980). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Lys437*) in the ALDH3A2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ALDH3A2 are known to be pathogenic (PMID: 10577908, 10854114). |
Department of Rehabilitation Medicine, |
RCV000757940 | SCV000882774 | pathogenic | Sjögren-Larsson syndrome | 2019-02-11 | no assertion criteria provided | research | The proband has another variant, NM_000382.2: c.1291_1292del (p.Lys431Glufs*5). |