Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Molecular Genetics, |
RCV002051791 | SCV002318406 | likely pathogenic | Neonatal diabetes mellitus | criteria provided, single submitter | clinical testing | ||
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000020291 | SCV005394448 | pathogenic | Permanent neonatal diabetes mellitus | 2024-09-13 | criteria provided, single submitter | clinical testing | Variant summary: ABCC8 c.674T>C (p.Leu225Pro) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251496 control chromosomes. c.674T>C has been reported in the literature at a heterozygous state in multiple individuals affected with Neonatal Diabetes Mellitus (example, Masia_2007, Garcin_2020, Gopi_2021). These data indicate that the variant is likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in about 4-fold over-activated current in Mg nucleotides in COS cells (Masia_2007). The following publications have been ascertained in the context of this evaluation (PMID: 32418263, 32893419, 17317760). ClinVar contains an entry for this variant (Variation ID: 21170). Based on the evidence outlined above, the variant was classified as pathogenic. |
Gene |
RCV000020291 | SCV000040652 | not provided | Permanent neonatal diabetes mellitus | no assertion provided | literature only |