Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003317877 | SCV004021012 | likely benign | not specified | 2023-06-28 | criteria provided, single submitter | clinical testing | Variant summary: GLUD1 c.1063C>T (p.His355Tyr) results in a conservative amino acid change located in the C-terminal domain (IPR006096) 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 3.5e-05 in 396240 control chromosomes, predominantly at a frequency of 0.00026 (i.e., 14 heterozygotes) within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 416 fold of the estimated maximal expected allele frequency for a pathogenic variant in GLUD1 causing Congenital Hyperinsulinism phenotype (6.3e-07), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. To our knowledge, no occurrence of c.1063C>T in individuals affected with Congenital Hyperinsulinism and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely benign. |
| Institute of Human Genetics, |
RCV003455797 | SCV004177275 | uncertain significance | Hyperinsulinism-hyperammonemia syndrome | criteria provided, single submitter | not provided |