ClinVar Miner

Submissions for variant NM_000478.6(ALPL):c.1268T>C (p.Val423Ala)

dbSNP: rs2148192552
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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 RCV001999288 SCV002287439 likely pathogenic not provided 2021-10-04 criteria provided, single submitter clinical testing This sequence change replaces valine with alanine at codon 423 of the ALPL protein (p.Val423Ala). The valine residue is weakly conserved and there is a small physicochemical difference between valine and alanine. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individual(s) with hypophosphatasia (PMID: 11438998, 20089612). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as TNSALP 1268T>C V406A. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Not Available"). Experimental studies have shown that this missense change affects ALPL function (PMID: 11438998, 18422967). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Baylor Genetics RCV003471247 SCV004193664 pathogenic Adult hypophosphatasia 2023-10-24 criteria provided, single submitter clinical testing

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