ClinVar Miner

Submissions for variant NM_000478.6(ALPL):c.659G>C (p.Gly220Ala)

dbSNP: rs1644592603
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001389956 SCV001591516 pathogenic not provided 2023-10-17 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 220 of the ALPL protein (p.Gly220Ala). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with autosomal recessive hypophosphatasia (PMID: 12815606, 22394703, 28663156). This variant is also known as p.Gly203Ala. ClinVar contains an entry for this variant (Variation ID: 1076161). 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 disrupts the p.Gly220 amino acid residue in ALPL. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 22397652, 25731960). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
JKU Lab, Dept of Paediatrics, Johannes Kepler University RCV001831402 SCV004175186 pathogenic Hypophosphatasia 2023-10-24 criteria provided, single submitter clinical testing Absent in GnomAD. Further information about the ACMG criteria applied can be looked up in the ALPL gene variant database. https://alplmutationdatabase.jku.at/
Baylor Genetics RCV003473995 SCV004194897 pathogenic Adult hypophosphatasia 2023-08-02 criteria provided, single submitter clinical testing
Natera, Inc. RCV001831402 SCV002094066 pathogenic Hypophosphatasia 2020-11-13 no assertion criteria provided clinical testing

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