Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Genetic Services Laboratory, |
RCV000500391 | SCV000595310 | likely pathogenic | Hyperinsulinemic hypoglycemia, familial, 2 | 2015-02-13 | criteria provided, single submitter | clinical testing | |
| Clinical Genomics, |
RCV002227171 | SCV002505932 | uncertain significance | Hyperinsulinemia | criteria provided, single submitter | research | Mutations in KCNJ 11 gene can cause decreased production and secretion of insulin. This can lead to MODY which may be responsive to oral sulfonylureas. However, this particular variant (rs750414160) of KCNJ11 gene can inactivate KATP channels that can inturn lead to hyperinsulinemia. More studies are required to ascertain the role of this particular variant (rs750414160) in MODY. | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003993989 | SCV004813641 | likely pathogenic | Familial hyperinsulinism | 2024-02-22 | criteria provided, single submitter | clinical testing | Variant summary: KCNJ11 c.868G>A (p.Val290Met) results in a conservative amino acid change located in the Inward rectifier potassium channel, C-terminal (IPR041647) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2e-05 in 251416 control chromosomes. c.868G>A has been reported in the literature either at a homozygous state or at a heterozygous state in at-least two unrelated individuals affected with Familial Hyperinsulinism (example, Loechner_2011, Maiorana_2014). In the family with a proband carrying the homozygous variant, two of clinically unaffected carriers with the heterozygous variant reported abnormally enhanced glucose tolerance. This variant, at a heterozygous state was also identified in patients with type 1 diabetes and unspecified carrier(s) without Diabetes (Sanyoura_2018, Billings_2022). These data indicate that the variant may be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in diminished Potassium channel activity when expressed homomerically, and to a lesser extent (about 50%) when expressed heteromerically with wild-type subunit in COSm6 cells (Loechner_2011), suggesting of a loss-of-function variant. The following publications have been ascertained in the context of this evaluation (PMID: 36208030, 20980454, 24383515, 28938416). ClinVar contains an entry for this variant (Variation ID: 435556). Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Baylor Genetics | RCV004568634 | SCV005059785 | likely pathogenic | Type 2 diabetes mellitus | 2024-03-30 | criteria provided, single submitter | clinical testing |