Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001999288 | SCV002287439 | likely pathogenic | not provided | 2021-10-04 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). 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. Experimental studies have shown that this missense change affects ALPL function (PMID: 11438998, 18422967). 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"). This variant is also known as TNSALP 1268T>C V406A. 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 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. |
| Baylor Genetics | RCV003471247 | SCV004193664 | pathogenic | Adult hypophosphatasia | 2023-10-24 | criteria provided, single submitter | clinical testing |