ClinVar Miner

Submissions for variant NM_001089.3(ABCA3):c.128G>A (p.Arg43His) (rs754714105)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000221771 SCV000271306 pathogenic Primary interstitial lung disease specific to childhood due to pulmonary surfactant protein anomalies 2015-02-26 criteria provided, single submitter clinical testing The p.Arg43His variant in ABCA3 has been previously reported in 1 homozygous inf ant with interstitial lung disease (ILD) and in 3 compound heterozygous infants/ children with ILD (Doan 2008, Agrawal 2012, Wambach 2014). In addition, two othe r variants at this codon (p.Arg43Leu and p.Arg43Cys) have each been reported in 2 compound heterozygous children with ILD and one of these variants (p.Arg43Cys) segregated with disease in an affected relative, suggesting that changes to thi s residue are not tolerated (Brasch 2006, Garmany 2006, Agrawal 2012, Wambach 20 14). The p.Arg43His variant has been identified in 1/66674 European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org). Alth ough this variant has been seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. Computational predic tion tools and conservation analysis do not provide strong support for or agains t an impact the protein. In summary, this variant meets our criteria to be class ified as pathogenic for ILD in an autosomal recessive manner(http://www.partners .org/personalizedmedicine/LMM).

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