ClinVar Miner

Submissions for variant NM_000031.6(ALAD):c.36C>G (p.Phe12Leu)

gnomAD frequency: 0.00004  dbSNP: rs121912984
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx 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

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