Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genetic Services Laboratory, |
RCV000192330 | SCV000247658 | pathogenic | Hyperinsulinemic hypoglycemia, familial, 2 | 2015-05-18 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001385879 | SCV001585887 | pathogenic | not provided | 2024-01-11 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 294 of the KCNJ11 protein (p.Thr294Met). This variant is present in population databases (rs780957825, gnomAD 0.01%). This missense change has been observed in individuals with autosomal recessive diffuse or paternally inherited focal hyperinsulinism (PMID: 20049716, 20589481, 20685672, 24434300). ClinVar contains an entry for this variant (Variation ID: 211230). 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 KCNJ11 protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects KCNJ11 function (PMID: 20049716). For these reasons, this variant has been classified as Pathogenic. |
Fulgent Genetics, |
RCV001535984 | SCV001752654 | likely pathogenic | Diabetes mellitus, transient neonatal, 3; Hyperinsulinemic hypoglycemia, familial, 2; Type 2 diabetes mellitus; Maturity-onset diabetes of the young type 13; Diabetes mellitus, permanent neonatal 2 | 2021-06-30 | criteria provided, single submitter | clinical testing | |
Clinical Genomics, |
RCV002227091 | SCV002506483 | uncertain risk allele | Hyperinsulinemia | criteria provided, single submitter | research | Mutations in KCNJ11 gene can cause decreased production and secretion of insulin. This can lead to MODY which may be responsive to oral sulfonylureas. This particular variant (rs780957825) is associated with Familial hyperinsulinemic hypoglycemia and response to diazoxide therapy. | |
Baylor Genetics | RCV003462300 | SCV004198064 | likely pathogenic | Type 2 diabetes mellitus | 2023-05-23 | criteria provided, single submitter | clinical testing | |
Counsyl | RCV000984004 | SCV000793561 | likely pathogenic | Diabetes mellitus, transient neonatal, 3 | 2017-08-18 | no assertion criteria provided | clinical testing | |
Clinical Genomics, |
RCV002227090 | SCV002506481 | uncertain significance | Maturity onset diabetes mellitus in young | flagged submission | research | Mutations in KCNJ11 gene can cause decreased production and secretion of insulin. This can lead to MODY which may be responsive to oral sulfonylureas. This particular variant (rs780957825) is associated with Familial hyperinsulinemic hypoglycemia and response to diazoxide therapy. However, no sufficient evidence is found to ascertain the significance of rs780957825 in MODY yet. |