Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000672033 | SCV000797088 | uncertain significance | Hyperinsulinemic hypoglycemia, familial, 1 | 2018-01-11 | criteria provided, single submitter | clinical testing | |
| Fulgent Genetics, |
RCV002507174 | SCV002816152 | uncertain significance | Diabetes mellitus, transient neonatal, 2; Hyperinsulinemic hypoglycemia, familial, 1; Leucine-induced hypoglycemia; Type 2 diabetes mellitus; Diabetes mellitus, permanent neonatal 3 | 2021-12-27 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV002531303 | SCV003439585 | likely pathogenic | not provided | 2023-07-21 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Experimental studies have shown that this missense change affects ABCC8 function (PMID: 17668386). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ABCC8 protein function. ClinVar contains an entry for this variant (Variation ID: 556086). This missense change has been observed in individuals with autosomal recessive neonatal diabetes (PMID: 17668386, 17919176). This variant is present in population databases (rs768017509, gnomAD 0.002%). This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 229 of the ABCC8 protein (p.Thr229Ile). |
| Baylor Genetics | RCV003459633 | SCV004197719 | likely pathogenic | Type 2 diabetes mellitus | 2023-08-13 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003987660 | SCV004803554 | uncertain significance | not specified | 2024-01-22 | criteria provided, single submitter | clinical testing | Variant summary: ABCC8 c.686C>T (p.Thr229Ile) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 251488 control chromosomes (gnomAD). c.686C>T has been reported in the literature in the homozygous state in an individual affected with transient neonatal diabetes mellitus and in the compound heterozygous state with p.V1523L in an individual with permanent diabetes mellitus (Ellard_2007, Patch_2007). These data indicate that the variant may be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function using Xenopus oocytes with the variant in either the heterozygous state or the compound heterozygous state with p.V1523L, finding that the variant results in reduced ATP sensitivity (Ellard_2007). The following publications have been ascertained in the context of this evaluation (PMID: 17668386, 17919176). ClinVar contains an entry for this variant (Variation ID: 556086). Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. |