ClinVar Miner

Submissions for variant NM_001080.3(ALDH5A1):c.621del (p.Ser208fs)

dbSNP: rs1306678453
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000822905 SCV000963729 pathogenic Succinate-semialdehyde dehydrogenase deficiency 2024-01-08 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser208Valfs*3) in the ALDH5A1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ALDH5A1 are known to be pathogenic (PMID: 14635103). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with succinate semialdehyde dehydrogenase deficiency (PMID: 14635103). ClinVar contains an entry for this variant (Variation ID: 664746). For these reasons, this variant has been classified as Pathogenic.
DASA RCV000822905 SCV002567977 pathogenic Succinate-semialdehyde dehydrogenase deficiency 2022-08-10 criteria provided, single submitter clinical testing The c.621del;p.(Ser208Valfs*3) is a null frameshift variant (NMD) in the ALDH5A1 gene and predicts alteration of the nonsense-mediate decay - NMD is present in a relevant exon to the transcript - PVS1.This sequence change has been observed in affected individual(s) and ClinVar contains an entry for this variant(ClinVar ID: 664746; PMID: 14635103, 32395407) - PS4. The variant is present at low allele frequencies population databases (rs1306678453 – gnomAD 0.00006571%; ABraOM no frequency - https://abraom.ib.usp.br/) -PM2_supporting.The p.(Ser208Valfs*3) was detected in trans with a pathogenic variant (PMID: 14635103; 32395407) - PM3. In summary, the currently available evidence indicates that the variant is pathogenic.
Elsea Laboratory, Baylor College of Medicine RCV000822905 SCV002819989 pathogenic Succinate-semialdehyde dehydrogenase deficiency 2021-03-08 criteria provided, single submitter curation
GeneDx RCV004702462 SCV005201960 pathogenic not provided 2023-05-25 criteria provided, single submitter clinical testing Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 14635103, 32395407)

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