ClinVar Miner

Submissions for variant NM_000235.4(LIPA):c.746C>T (p.Thr249Ile)

gnomAD frequency: 0.00001  dbSNP: rs373857537
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV002563853 SCV001408983 uncertain significance Wolman disease 2021-09-02 criteria provided, single submitter clinical testing This sequence change replaces threonine with isoleucine at codon 249 of the LIPA protein (p.Thr249Ile). The threonine residue is weakly conserved and there is a moderate physicochemical difference between threonine and isoleucine. This variant is present in population databases (rs373857537, ExAC 0.009%). This variant has not been reported in the literature in individuals affected with LIPA-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
New York Genome Center RCV001236267 SCV003925222 uncertain significance Lysosomal acid lipase deficiency 2022-07-08 criteria provided, single submitter clinical testing
Natera, Inc. RCV001236267 SCV002091355 uncertain significance Lysosomal acid lipase deficiency 2020-12-05 no assertion criteria provided clinical testing

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