Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003401279 | SCV004122448 | uncertain significance | not specified | 2023-10-31 | criteria provided, single submitter | clinical testing | Variant summary: ALPL c.1454C>T (p.Ala485Val) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 243370 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1454C>T in individuals affected with Hypophosphatasia and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Labcorp Genetics |
RCV005055838 | SCV005723464 | likely pathogenic | not provided | 2024-08-19 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 485 of the ALPL protein (p.Ala485Val). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of hypophosphatasia (Internal data). ClinVar contains an entry for this variant (Variation ID: 291309). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt ALPL protein function with a positive predictive value of 95%. 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. |
| Institute of Human Genetics, |
RCV000346514 | SCV000346028 | likely pathogenic | Decreased circulating alkaline phosphatase activity | no assertion criteria provided | clinical testing |