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NM_000540.3(RYR1):c.6617C>T (p.Thr2206Met) AND King Denborough syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Aug 1, 2002
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV001729348.10

Allele description [Variation Report for NM_000540.3(RYR1):c.6617C>T (p.Thr2206Met)]

NM_000540.3(RYR1):c.6617C>T (p.Thr2206Met)

Gene:
RYR1:ryanodine receptor 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
19q13.2
Genomic location:
Preferred name:
NM_000540.3(RYR1):c.6617C>T (p.Thr2206Met)
Other names:
NM_000540.3(RYR1):c.6617C>T
HGVS:
  • NC_000019.10:g.38496283C>T
  • NG_008866.1:g.67584C>T
  • NM_000540.3:c.6617C>TMANE SELECT
  • NM_001042723.2:c.6617C>T
  • NP_000531.2:p.Thr2206Met
  • NP_000531.2:p.Thr2206Met
  • NP_001036188.1:p.Thr2206Met
  • LRG_766t1:c.6617C>T
  • LRG_766:g.67584C>T
  • LRG_766p1:p.Thr2206Met
  • NC_000019.9:g.38986923C>T
  • NM_000540.2:c.6617C>T
  • NM_000540.3:c.6617C>T
  • P21817:p.Thr2206Met
  • p.(Thr2206Met)
Protein change:
T2206M; THR2206MET
Links:
UniProtKB: P21817#VAR_005604; OMIM: 180901.0014; dbSNP: rs118192177
NCBI 1000 Genomes Browser:
rs118192177
Molecular consequence:
  • NM_000540.3:c.6617C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001042723.2:c.6617C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
King Denborough syndrome (KDS)
Synonyms:
King syndrome
Identifiers:
MONDO: MONDO:0020485; MedGen: C1840365; OMIM: 619542

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001977101OMIM
no assertion criteria provided
Pathogenic
(Aug 1, 2002) 		germlineliterature only

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Identification of novel mutations in the ryanodine-receptor gene (RYR1) in malignant hyperthermia: genotype-phenotype correlation.

Manning BM, Quane KA, Ording H, Urwyler A, Tegazzin V, Lehane M, O'Halloran J, Hartung E, Giblin LM, Lynch PJ, Vaughan P, Censier K, Bendixen D, Comi G, Heytens L, Monsieurs K, Fagerlund T, Wolz W, Heffron JJ, Muller CR, McCarthy TV.

Am J Hum Genet. 1998 Mar;62(3):599-609.

PubMed [citation]
PMID:
9497245
PMCID:
PMC1376943

Increased sensitivity to 4-chloro-m-cresol and caffeine in primary myotubes from malignant hyperthermia susceptible individuals carrying the ryanodine receptor 1 Thr2206Met (C6617T) mutation.

Wehner M, Rueffert H, Koenig F, Neuhaus J, Olthoff D.

Clin Genet. 2002 Aug;62(2):135-46.

PubMed [citation]
PMID:
12220451
See all PubMed Citations (3)

Details of each submission

From OMIM, SCV001977101.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (3)

Description

Malignant Hyperthermia, Susceptibility to, 1

In affected members of a family with malignant hyperthermia (MHS1; 145600), Manning et al. (1998) identified a heterozygous c.6617C-T transition in the RYR1 gene, resulting in a thr2206-to-met (T2206M) substitution.

Wehner et al. (2002) identified the T2206M mutation in patients with MHS. Myotubes derived from individuals with the T2206M mutation had an abnormal response of the intracellular calcium concentration to 4-chloro-m-cresol and to caffeine. In myotubes, the EC50 for 4-chloro-m-cresol and for caffeine was reduced strikingly, indicating that this mutation is pathogenic for malignant hyperthermia.

King-Denborough Syndrome

In a 6-year-old boy (patient 1) with King-Denborough syndrome (KDS; 619542), Dowling et al. (2011) identified heterozygosity for the c.6617C-T transition in exon 40 of the RYR1 gene, resulting in a T2206M substitution. The mutation was identified by RYR1 gene sequencing. Western blot analysis in patient muscle tissue showed an 84% reduction in RyR1 protein level compared to control.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 26, 2024