ClinVar Miner

Submissions for variant NM_000525.4(KCNJ11):c.761C>T (p.Pro254Leu)

gnomAD frequency: 0.00001  dbSNP: rs104894237
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002512937 SCV003439573 likely pathogenic not provided 2023-10-22 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 254 of the KCNJ11 protein (p.Pro254Leu). This variant is present in population databases (rs104894237, gnomAD 0.003%). This missense change has been observed in individuals with autosomal recessive hyperinsulinism (PMID: 15579781, 27188453). ClinVar contains an entry for this variant (Variation ID: 8675). 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. Experimental studies have shown that this missense change affects KCNJ11 function (PMID: 15579781). 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.
Baylor Genetics RCV003466840 SCV004198051 likely pathogenic Type 2 diabetes mellitus 2023-09-23 criteria provided, single submitter clinical testing
OMIM RCV000009210 SCV000029428 pathogenic Hyperinsulinemic hypoglycemia, familial, 2 2004-12-01 no assertion criteria provided literature only
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic RCV002226640 SCV002505433 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. It is also associated with Neonatal Diabetes. However, no sufficient evidence is found to ascertain the role of rs104894237 variant in MODY yet.

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