ClinVar Miner

Submissions for variant NM_000382.3(ALDH3A2):c.682C>T (p.Arg228Cys)

gnomAD frequency: 0.00002  dbSNP: rs72547566
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000672596 SCV000797711 likely pathogenic Sjögren-Larsson syndrome 2018-02-07 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001383429 SCV001582570 pathogenic not provided 2023-10-14 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 228 of the ALDH3A2 protein (p.Arg228Cys). This variant is present in population databases (rs72547566, gnomAD 0.003%). This missense change has been observed in individuals with Sjögren–Larsson syndrome (PMID: 10577908, 27717089, 28257279, 28471629, 30925032). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 556574). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects ALDH3A2 function (PMID: 10577908). This variant disrupts the p.Arg228 amino acid residue in ALDH3A2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 22397046, 29704247). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV001383429 SCV002099564 pathogenic not provided 2022-02-24 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect with significant loss of enzyme activity for the R228C mutant at 9% of the wild-type activity (Rizzo et al., 1999); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 16476818, 10577908, 30925032, 31456290, 16837225, 28257279, 28471629, 25047030, 27717089, 32395410)
Fulgent Genetics, Fulgent Genetics RCV000672596 SCV002775173 pathogenic Sjögren-Larsson syndrome 2022-01-17 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000672596 SCV003799962 pathogenic Sjögren-Larsson syndrome 2022-03-10 criteria provided, single submitter clinical testing
Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital RCV000672596 SCV005420486 pathogenic Sjögren-Larsson syndrome 2024-10-04 criteria provided, single submitter research PS3,PM3,PP1,PM2,PP3,PM5
Sharon lab, Hadassah-Hebrew University Medical Center RCV000672596 SCV001160895 likely pathogenic Sjögren-Larsson syndrome 2019-06-23 no assertion criteria provided research
Natera, Inc. RCV000672596 SCV002093179 pathogenic Sjögren-Larsson syndrome 2017-08-02 no assertion criteria provided clinical testing

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