ClinVar Miner

Submissions for variant NM_001182.5(ALDH7A1):c.34del (p.Ala12fs) (rs750693623)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000717913 SCV000848773 pathogenic Seizures 2017-01-17 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense),Rare (0.1%) in general population databases (dbsnp, esp, 1000 genomes)
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000732134 SCV000860044 uncertain significance not provided 2018-03-23 criteria provided, single submitter clinical testing
GeneDx RCV000732134 SCV000491045 uncertain significance not provided 2017-11-28 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the ALDH7A1 gene. The c.34delG variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The c.34delG variant causes a frameshift starting with codon Alanine 12, changes this amino acid to a Leucine residue, and creates a premature Stop codon at position 31 of the new reading frame, denoted p.Ala12LeufsX31. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. However, the c.34delG variantis observed in 20/16646 (0.12%) alleles from individuals of African background in large populationcohorts (Lek et al., 2016). Therefore, based on the currently available information, it is unclearwhether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000548007 SCV000640320 pathogenic Pyridoxine-dependent epilepsy 2018-12-18 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ala12Leufs*31) in the ALDH7A1 gene. It is expected to result in an absent or disrupted protein product. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with ALDH7A1-related disease. ClinVar contains an entry for this variant (Variation ID: 372663). Loss-of-function variants in ALDH7A1 are known to be pathogenic (PMID: 16491085). For these reasons, this variant has been classified as Pathogenic.

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