Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genetic Services Laboratory, |
RCV000193805 | SCV000247485 | likely pathogenic | Hyperinsulinism-hyperammonemia syndrome | 2015-05-22 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV003479053 | SCV004223543 | uncertain significance | not specified | 2023-11-08 | criteria provided, single submitter | clinical testing | Variant summary: GLUD1 c.1498G>A (p.Ala500Thr) results in a non-conservative amino acid change located in the Glutamate/phenylalanine/leucine/valine/L-tryptophan dehydrogenase, C-terminal domain (IPR006096) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251286 control chromosomes (gnomAD). c.1498G>A (also known as p.Ala447Thr) has been reported in the literature in individuals affected with Congenital Hyperinsulinism (examples: Stanley_2000, Faletra_2013, and Hopkins_2023). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 23506826, 36239000, 10871207). One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. |