Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003560873 | SCV004295391 | pathogenic | not provided | 2023-06-09 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 1526017). This premature translational stop signal has been observed in individual(s) with autosomal recessive diffuse or paternally inherited focal hyperinsulinism (PMID: 25117148, 30386300). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln444*) in the ABCC8 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ABCC8 are known to be pathogenic (PMID: 20685672, 23345197). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003388087 | SCV004099978 | pathogenic | Familial hyperinsulinism | 2023-09-19 | criteria provided, single submitter | clinical testing | Variant summary: ABCC8 c.1330C>T (p.Gln444X) results in a premature termination codon, predicted to cause absence of the protein due to nonsense mediated decay, a commonly known mechanism for disease. The variant was absent in 251458 control chromosomes (gnomAD). c.1330C>T has been reported in the literature in at least two individuals affected with Congenital Hyperinsulinism (e.g. Sharma_2022). These data indicate that the variant is likely associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 34992182). 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 pathogenic. |
| Molecular Genetics, |
RCV002052037 | SCV002318431 | pathogenic | Hyperinsulinemic hypoglycemia, familial, 1 | criteria provided, single submitter | clinical testing |