ClinVar Miner

Submissions for variant NM_000478.6(ALPL):c.673T>C (p.Tyr225His)

gnomAD frequency: 0.00003  dbSNP: rs759125473
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000393235 SCV000340788 uncertain significance not provided 2016-03-30 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002494864 SCV002784335 uncertain significance Adult hypophosphatasia; Childhood hypophosphatasia; Infantile hypophosphatasia 2022-05-18 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000393235 SCV003448785 pathogenic not provided 2024-01-29 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with histidine, which is basic and polar, at codon 225 of the ALPL protein (p.Tyr225His). This variant is present in population databases (rs759125473, gnomAD 0.004%). This missense change has been observed in individual(s) with clinical features of hypophosphatasia (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 287114). 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 with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.
Undiagnosed Diseases Network, NIH RCV002509350 SCV002818569 uncertain significance Adult hypophosphatasia 2022-06-24 no assertion criteria provided clinical testing

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