Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000169412 | SCV000220816 | likely pathogenic | Infantile hypophosphatasia | 2014-10-21 | criteria provided, single submitter | literature only | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001582665 | SCV001821321 | pathogenic | Hypophosphatasia | 2021-08-20 | criteria provided, single submitter | clinical testing | Variant summary: ALPL c.809G>A (p.Trp270X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 8e-06 in 251350 control chromosomes. c.809G>A has been reported in the literature in individuals affected with Hypophosphatasia, including two lethal cases who were compound heterozygous as well as an adult case who was heterozygous for the variant (Mornet_1998, Tailandier_2017, Angle_2020). The variant was found to have 1.2% of wild-type activity in transfection studies (Zurutuza_1999). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic. |
Invitae | RCV002515199 | SCV003523164 | pathogenic | not provided | 2023-12-30 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Trp270*) in the ALPL gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ALPL are known to be pathogenic (PMID: 3174660, 10679946, 32973344, 33814268). This variant is present in population databases (rs786204634, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with hypophosphatasia (PMID: 9781036). ClinVar contains an entry for this variant (Variation ID: 189023). For these reasons, this variant has been classified as Pathogenic. |
Baylor Genetics | RCV003468843 | SCV004192550 | pathogenic | Adult hypophosphatasia | 2023-08-08 | criteria provided, single submitter | clinical testing | |
Natera, |
RCV001582665 | SCV002094075 | pathogenic | Hypophosphatasia | 2021-07-20 | no assertion criteria provided | clinical testing |