ClinVar Miner

Submissions for variant NM_000525.4(KCNJ11):c.560C>T (p.Ala187Val)

gnomAD frequency: 0.00001  dbSNP: rs1371185696
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000666176 SCV000790423 likely pathogenic Permanent neonatal diabetes mellitus; Diabetes mellitus, transient neonatal, 3; Hyperinsulinemic hypoglycemia, familial, 2 2017-03-21 criteria provided, single submitter clinical testing
Invitae RCV001868211 SCV002280896 pathogenic not provided 2023-10-03 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 187 of the KCNJ11 protein (p.Ala187Val). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with autosomal recessive congenital hyperinsulinism and/or focal congenital hyperinsulinism (PMID: 11395395, 21422196, 21812132). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 551187). 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. This variant disrupts the p.Ala187 amino acid residue in KCNJ11. Other variant(s) that disrupt this residue have been observed in individuals with KCNJ11-related conditions (PMID: 21422196, 23652837), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic RCV002227197 SCV002506470 uncertain significance Maturity onset diabetes mellitus in young 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. It is also associated with Neonatal Diabetes. However, no sufficient evidence is found to ascertain the role of this particular variant (rs1371185696) in MODY yet.

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