ClinVar Miner

Submissions for variant NM_014336.5(AIPL1):c.421C>T (p.Gln141Ter)

gnomAD frequency: 0.00002  dbSNP: rs200125117
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001172388 SCV002246682 pathogenic Leber congenital amaurosis 4 2023-11-20 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln141*) in the AIPL1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in AIPL1 are known to be pathogenic (PMID: 10615133, 15249368, 15347646). This variant is present in population databases (rs200125117, gnomAD 0.03%). This premature translational stop signal has been observed in individuals with inherited retinal dystrophy (PMID: 25356976, 30029497). ClinVar contains an entry for this variant (Variation ID: 916622). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003987790 SCV004803964 pathogenic Leber congenital amaurosis 2024-01-29 criteria provided, single submitter clinical testing Variant summary: AIPL1 c.421C>T (p.Gln141X) 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. The variant allele was found at a frequency of 2.4e-05 in 249644 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.421C>T has been reported in the literature in both homozygous and compound heterozygous individuals affected with Leber Congenital Amaurosis (e.g., Xu_2020). These data indicate that the variant is very likely to be associated with disease. The following publication was ascertained in the context of this evaluation (PMID: 31630094). ClinVar contains an entry for this variant (Variation ID: 916622). Based on the evidence outlined above, the variant was classified as pathogenic.
Laboratory of Genetics in Ophthalmology, Institut Imagine RCV001172388 SCV001335446 pathogenic Leber congenital amaurosis 4 no assertion criteria provided research

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