ClinVar Miner

Submissions for variant NM_001182.5(ALDH7A1):c.494G>C (p.Gly165Ala)

gnomAD frequency: 0.00040  dbSNP: rs375491094
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000724449 SCV000231000 uncertain significance not provided 2015-01-07 criteria provided, single submitter clinical testing
GeneDx RCV000724449 SCV000240329 uncertain significance not provided 2024-04-25 criteria provided, single submitter clinical testing In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Illumina Laboratory Services, Illumina RCV001156822 SCV001318351 uncertain significance Pyridoxine-dependent epilepsy 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Labcorp Genetics (formerly Invitae), Labcorp RCV001156822 SCV002470097 likely benign Pyridoxine-dependent epilepsy 2024-01-31 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV001156822 SCV004239000 uncertain significance Pyridoxine-dependent epilepsy 2023-11-02 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004586599 SCV005077520 likely benign not specified 2024-04-04 criteria provided, single submitter clinical testing Variant summary: ALDH7A1 c.494G>C (p.Gly165Ala) results in a non-conservative amino acid change located in the Aldehyde dehydrogenase domain (IPR015590) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0004 in 251418 control chromosomes, predominantly at a frequency of 0.0032 within the South Asian subpopulation in the gnomAD database. The observed variant frequency within South Asian control individuals in the gnomAD database is approximately 1.8 fold of the estimated maximal expected allele frequency for a pathogenic variant in ALDH7A1 causing Pyridoxine-Dependent Epilepsy phenotype (0.0018), strongly suggesting that the variant is a benign polymorphism found primarily in populations of South Asian origin. To our knowledge, no occurrence of c.494G>C in individuals affected with Pyridoxine-Dependent Epilepsy and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 197721). Based on the evidence outlined above, the variant was classified as likely benign.

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