Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Unidad de Genómica Médica UC, |
RCV000007009 | SCV000902518 | pathogenic | Congenital generalized lipodystrophy type 1 | 2013-03-04 | criteria provided, single submitter | research | Congenital generalized lipodystrophy (CGL) is a rare autosomal recessive disorder characterized by extreme reduction of white adipose tissue (WAT) mass. CGL type 1 is the most frequent form and is caused by mutations in AGPAT2. Genetic and clinical studies were performed in two affected sisters of a Chilean family. These patients have notoriously dissimilar metabolic abnormalities that correlate with differential levels of circulating leptin and soluble leptin receptor fraction. Sequencing of AGPAT2 exons and exon-intron boundaries revealed two homozygous mutations in both sisters. Intronic c.493-1G>C mutation destroy a conserved splicing site that likely leads to exon 4 skipping and deletion of whole AGPAT2 substrate binding domain. In silico protein modeling provided insights of the mechanisms of lack of catalytic activity owing to both mutations. |
DASA | RCV000007009 | SCV002073789 | likely pathogenic | Congenital generalized lipodystrophy type 1 | 2022-02-05 | criteria provided, single submitter | clinical testing | The c.493-1G>C variant is located in a canonical splice-site, and it is not predicted the protein reading frame alteration, however, occur in a critical region and the variant disrupts <10% of protein - PVS1_moderate. This sequence change has been observed in affected individual(s) and ClinVar contains an entry for this variant (ClinVar ID: 6630; PMID: 24498038, 15181077) - PS4_supporting. The variant is present at low allele frequencies population databases (rs606231168 – gnomAD 0.00006570%; ABraOM no frequency - http://abraom.ib.usp.br/) - PM2_supporting. The c.493-1G>C was detected in trans with a pathogenic variant (PMID: 24498038) - PM3. In summary, the currently available evidence indicates that the variant is likely pathogenic. |
OMIM | RCV000007009 | SCV000027205 | pathogenic | Congenital generalized lipodystrophy type 1 | 2004-06-01 | no assertion criteria provided | literature only | |
Gene |
RCV000007009 | SCV000490119 | not provided | Congenital generalized lipodystrophy type 1 | no assertion provided | literature only |