Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
New York Genome Center | RCV003227950 | SCV003925307 | uncertain significance | Hyperinsulinemic hypoglycemia, familial, 1 | 2022-09-16 | criteria provided, single submitter | clinical testing | The c.3661C>T p.(Arg1221Trp) variant in the ABCC8 gene has previously been reported in an individual with early onset diabetes (Proband P-6, age at diagnosis: 27 years, PMID: 33300273] and it has been deposited in ClinVar [ClinVar ID: 989961] as Variant of Uncertain Significance. The c.3661C>T variant is observed in 3 alleles (~0.0004% minor allele frequency with 0 homozygotes) in population databases (gnomAD v2.1.1 and v3.1.2, TOPMed Freeze8), suggesting it is not a common benign variant in the populations represented in those databases. The c.3661C>T variant in ABCC8 is located in exon 30 of this 39-exon gene, and predicted to replace an evolutionarily conserved arginine amino acid with tryptophan at position 1221 in the ABC transmembrane type-1 2 domainof the encoded protein. In silico predictions are in favor of damaging effect for p.(Arg1221Trp) [(CADD v1.6 = 32, REVEL = 0.736)]; however, there are no functional studies to support or refute these predictions. Based on available evidence this c.3661C>T p.(Arg1221Trp) variant identified in ABCC8 is classified as a Variant of Uncertain Significance. |
Natera, |
RCV001277869 | SCV001464848 | uncertain significance | Hereditary hyperinsulinism | 2020-08-28 | no assertion criteria provided | clinical testing |