Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003236542 | SCV003933787 | likely pathogenic | Leber congenital amaurosis | 2023-05-30 | criteria provided, single submitter | clinical testing | Variant summary: LRAT c.40_41delinsTT (p.Glu14Leu) results in a non-conservative amino acid change in the encoded protein sequence. Three of four in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251394 control chromosomes (gnomAD). c.40_41delinsTT has been reported in the literature in at least one homozygous individual affected with retinal dystrophy (DevBorman_2012, Scholl_2015). These data indicate that the variant maybe associated with disease. A publication reported experimental evidence evaluating an impact on protein function, demonstrating severely reduced protein levels likely due to protein instability with accelerated proteosomal degradation (Chelstowska_2017). The following publications have been ascertained in the context of this evaluation (PMID: 22570351, 26656277, 28758396, 31561851). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic. |