Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000413492 | SCV000491332 | likely pathogenic | not provided | 2023-08-11 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate that the p.(F12L) variant results in ALAD protein without significant enzyme activity (Maruno et al., 2001; Akagi et al., 1999; Inoue et al., 2008; Akagi et al., 2006); Variant was identified in the heterozygous state in several individuals from the same family with ALAD deficiency (Akagi et al., 1999); This variant is associated with the following publications: (PMID: 19015748, 17236137, 16398658, 11342419, 10519994) |
Invitae | RCV000413492 | SCV001398559 | uncertain significance | not provided | 2022-05-25 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 12 of the ALAD protein (p.Phe12Leu). This variant is present in population databases (rs121912984, gnomAD 0.006%). 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. Experimental studies have shown that this missense change affects ALAD function (PMID: 10519994, 17236137). 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 16867). This missense change has been observed in individual(s) with ALAD-related conditions (PMID: 10519994, 16398658; Invitae). |
OMIM | RCV000018363 | SCV000038642 | pathogenic | Porphyria, acute hepatic, digenic | 2006-01-01 | no assertion criteria provided | literature only |