NM_000525.4(KCNJ11):c.601C>T (p.Arg201Cys) AND Diabetes mellitus, permanent neonatal 2

Clinical significance:Pathogenic (Last evaluated: Jan 1, 2005)
Review status:(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

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Based on:: 1 submission [Details]
Record status:: current
Accession:: RCV001089465.3

Allele description [Variation Report for NM_000525.4(KCNJ11):c.601C>T (p.Arg201Cys)]

NM_000525.4(KCNJ11):c.601C>T (p.Arg201Cys)

Gene:

KCNJ11:potassium inwardly rectifying channel subfamily J member 11 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11p15.1

Genomic location:

Preferred name:

NM_000525.4(KCNJ11):c.601C>T (p.Arg201Cys)

HGVS:

NC_000011.10:g.17387491G>A
NG_012446.1:g.6169C>T
NM_000525.4:c.601C>TMANE SELECT
NM_001166290.2:c.340C>T
NM_001377296.1:c.340C>T
NM_001377297.1:c.340C>T
NP_000516.3:p.Arg201Cys
NP_000516.3:p.Arg201Cys
NP_001159762.1:p.Arg114Cys
NP_001364225.1:p.Arg114Cys
NP_001364226.1:p.Arg114Cys
NC_000011.9:g.17409038G>A
NM_000525.3:c.601C>T

Protein change:

R114C; ARG201CYS

Links:

OMIM: 600937.0004; dbSNP: rs80356625

NCBI 1000 Genomes Browser:

rs80356625

Molecular consequence:

NM_000525.4:c.601C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001166290.2:c.340C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001377296.1:c.340C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001377297.1:c.340C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Diabetes mellitus, permanent neonatal 2
Identifiers:: MONDO: MONDO:0030087; MedGen: C5394296; OMIM: 618856

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000029420	OMIM	no assertion criteria provided	Pathogenic (Jan 1, 2005)	germline	literature only	PubMed (4) [See all records that cite these PMIDs] 12524280, 15583126, 15580558, 15292329 Gloyn, A. L., Pearson, E. R., Antcliff, J. F., Proks, P., Bruining, G. J., Slingerland, A. S., Howard, N., Srinivasan, S., Silva, J. M. C. L., Molnes, J., Edghill, E. L., Frayling, T. M., and 13 others Activating mutations in the gene encoding the ATP-sensitive potassium-channel subunit Kir6.2 and permanent neonatal diabetes. New Eng. J. Med. 350: 1838-1849, 2004. Note: Erratum: New Eng. J. Med. 351: 1470 only, 2004.

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000029420

OMIM

no assertion criteria provided

Pathogenic
(Jan 1, 2005)

germline

literature only

PubMed (4)
[See all records that cite these PMIDs]

Gloyn, A. L., Pearson, E. R., Antcliff, J. F., Proks, P., Bruining, G. J., Slingerland, A. S., Howard, N., Srinivasan, S., Silva, J. M. C. L., Molnes, J., Edghill, E. L., Frayling, T. M., and 13 others Activating mutations in the gene encoding the ATP-sensitive potassium-channel subunit Kir6.2 and permanent neonatal diabetes. New Eng. J. Med. 350: 1838-1849, 2004. Note: Erratum: New Eng. J. Med. 351: 1470 only, 2004.

Summary from all submissions

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Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Molecular basis for Kir6.2 channel inhibition by adenine nucleotides.

Ribalet B, John SA, Weiss JN.

Biophys J. 2003 Jan;84(1):266-76.

PubMed [citation]

PMID:: 12524280
PMCID:: PMC1302608

Molecular basis of Kir6.2 mutations associated with neonatal diabetes or neonatal diabetes plus neurological features.

Proks P, Antcliff JF, Lippiat J, Gloyn AL, Hattersley AT, Ashcroft FM.

Proc Natl Acad Sci U S A. 2004 Dec 14;101(50):17539-44. Epub 2004 Dec 6.

PubMed [citation]

PMID:: 15583126
PMCID:: PMC536014

See all PubMed Citations (4)

Details of each submission

From OMIM, SCV000029420.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (4)

Description

In a patient with permanent neonatal diabetes mellitus (PNDM2; 618856), Gloyn et al. (2004) identified a heterozygous arg201-to-cys (R201C) mutation in the Kir6.2 gene. The patient was diagnosed at 4 weeks of age and had no additional neurologic or dysmorphic features. The arg201 residue lies close to the ATP-binding site and was implicated in ATP sensitivity (Ribalet et al., 2003).

Proks et al. (2004) stated that the 2 mutations in residue arg201, R201H (600937.0002) and R201C, which lie in the ATP-binding site of Kir6.2, cause milder PNDM disease without neurologic features; however, Massa et al. (2005) identified the R201C mutation in a patient with PNDM who also had muscle weakness and delayed motor development.

Gloyn et al. (2004) described a family in which 2 affected paternal half-sibs were heterozygous for the R201C mutation. Direct sequencing of leukocyte DNA showed that their clinically unaffected mothers and father were genotypically normal. Quantitative real-time PCR analysis of the father's leukocyte DNA detected no trace of mutant DNA. These results were consistent with the father being mosaic for the mutation, which was restricted to his germline. Gloyn et al. (2004) concluded that the high percentage of permanent neonatal diabetes cases due to de novo KCNJ11 mutations (Gloyn et al., 2004) suggests that germline mosaicism may be common.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Feb 7, 2023

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