Submissions for variant NM_000478.6(ALPL):c.431G>C (p.Gly144Ala)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003682700	SCV004413034	uncertain significance	not provided	2023-08-31	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 144 of the ALPL protein (p.Gly144Ala). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. 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 not been reported in the literature in individuals affected with ALPL-related conditions. This variant is not present in population databases (gnomAD no frequency).
JKU Lab, Dept of Paediatrics, Johannes Kepler University	RCV004554924	SCV005043799	uncertain significance	Hypophosphatasia	2024-04-09	criteria provided, single submitter	clinical testing	The variant is absent from GnomAD. The ACMG criteria can be looked up in the ALPL gene variant database. https://alplmutationdatabase.jku.at/