Submissions for variant NM_000382.3(ALDH3A2):c.1309A>T (p.Lys437Ter)

dbSNP: rs1567607328

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	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, Incheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea	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).