ClinVar Miner

Submissions for variant NM_000478.6(ALPL):c.677T>C (p.Met226Thr)

gnomAD frequency: 0.00002  dbSNP: rs752641050
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV002277788 SCV002564817 uncertain significance Osteogenesis imperfecta 2022-06-30 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV003560918 SCV004291727 pathogenic not provided 2023-08-01 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. 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. ClinVar contains an entry for this variant (Variation ID: 1702003). This missense change has been observed in individual(s) with hypophosphatasia (PMID: 17395561; Invitae). This variant is present in population databases (rs752641050, gnomAD 0.004%). This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 226 of the ALPL protein (p.Met226Thr).
GeneDx RCV003560918 SCV005626470 likely pathogenic not provided 2024-07-11 criteria provided, single submitter clinical testing 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: 17395561)

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