ClinVar Miner

Submissions for variant NM_000478.6(ALPL):c.815G>T (p.Arg272Leu)

dbSNP: rs781272386
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001972664 SCV002242995 pathogenic not provided 2020-12-06 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg272 amino acid residue in ALPL. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 17253930, 24378058, 24276437, 18559907). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. This sequence change replaces arginine with leucine at codon 272 of the ALPL protein (p.Arg272Leu). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and leucine. 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 ALPL protein function. This variant has been observed in individual(s) with autosomal recessive hypophosphatasia (PMID: 12815606, 28127875). It has also been observed to segregate with disease in related individuals. This variant is also known as R255L. This variant is present in population databases (rs781272386, ExAC 0.002%).
Baylor Genetics RCV003471180 SCV004193150 pathogenic Adult hypophosphatasia 2023-03-25 criteria provided, single submitter clinical testing

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