ClinVar Miner

Submissions for variant NM_000352.6(ABCC8):c.2171T>C (p.Leu724Pro)

dbSNP: rs1402090677
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Molecular Genetics, Madras Diabetes Research Foundation RCV002052038 SCV002318433 likely pathogenic Hyperinsulinemic hypoglycemia, familial, 1 criteria provided, single submitter clinical testing
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard RCV002052038 SCV004026544 uncertain significance Hyperinsulinemic hypoglycemia, familial, 1 2023-08-16 criteria provided, single submitter curation The p.Leu724Pro variant in ABCC8 has been previously reported in 2 individuals with hyperinsulinemic hypoglycemia (PMID: 26180531, 23345197), and has been seen in 0.0009% (1/113580) of European (non-Finish) chromosomes by the Genome Aggregation Database (gnomAD,; dbSNP: rs1402090677). Although this variant has been seen in the general population in a heterozygous state, its frequency is low enough to be consistent with a recessive carrier frequency. This variant has also been reported in ClinVar (Variation ID: 1526018) and has been interpreted as likely pathogenic by Molecular Genetics (Madras Diabetes Research Foundation). Of the 2 affected individuals, both of those were homozygotes, which increases the likelihood that the p.Leu724Pro variant is pathogenic (PMID: 26180531, 23345197). Computational prediction tools and conservation analyses suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, while there is some suspicion for a pathogenic role, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: PM3, PP3, PM2_supporting (Richards 2015).

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