ClinVar Miner

Submissions for variant NM_000382.3(ALDH3A2):c.551C>T (p.Thr184Met)

gnomAD frequency: 0.00003  dbSNP: rs72547562
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169091 SCV000220275 likely pathogenic Sjögren-Larsson syndrome 2014-04-29 criteria provided, single submitter literature only
GeneDx RCV000427449 SCV000516604 pathogenic not provided 2023-01-30 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect (<1% residual enzyme 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: 10577908, 11408337, 15931689, 19124283, 29302074, 32395410, 29181214)
Invitae RCV000427449 SCV000941834 pathogenic not provided 2023-12-19 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 184 of the ALDH3A2 protein (p.Thr184Met). This variant is present in population databases (rs72547562, gnomAD 0.005%). This missense change has been observed in individuals with Sjogren-Larsson syndrome (PMID: 10577908, 11408337, 17998529). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 188768). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ALDH3A2 protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects ALDH3A2 function (PMID: 10577908). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV000169091 SCV001163408 pathogenic Sjögren-Larsson syndrome criteria provided, single submitter clinical testing
Revvity Omics, Revvity Omics RCV000169091 SCV002024251 pathogenic Sjögren-Larsson syndrome 2019-06-19 criteria provided, single submitter clinical testing
Natera, Inc. RCV000169091 SCV001459271 pathogenic Sjögren-Larsson syndrome 2020-09-16 no assertion criteria provided clinical testing

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