ClinVar Miner

Submissions for variant NM_001089.3(ABCA3):c.537G>C (p.Trp179Cys)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003324415 SCV004029187 uncertain significance not specified 2023-07-28 criteria provided, single submitter clinical testing Variant summary: ABCA3 c.537G>C (p.Trp179Cys) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251496 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.537G>C has been reported in the literature in individuals affected with Pulmonary surfactant metabolism dysfunction (Garmany_2006, Wambach_2014, Turcu_2013). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 16641205, 23625987, 24871971). No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV003561301 SCV004296367 pathogenic not provided 2023-01-24 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. This missense change has been observed in individual(s) with pulmonary surfactant metabolism dysfunction (PMID: 16641205, 24871971). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tryptophan, which is neutral and slightly polar, with cysteine, which is neutral and slightly polar, at codon 179 of the ABCA3 protein (p.Trp179Cys).

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