NM_000548.3(TSC2):c.2714G>A (p.Arg905Gln) AND Tuberous sclerosis 2

Clinical significance:Pathogenic (Last evaluated: Aug 16, 2013)

Review status:1 star out of maximum of 4 stars

classified by single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000013212.15

Allele description [Variation Report for ]

NM_000548.3(TSC2):c.2714G>A (p.Arg905Gln)

Gene:
TSC2:tuberous sclerosis 2 [Gene - OMIM]
Variant type:
single nucleotide variant
Cytogenetic location:
16p13.3
Genomic location:
Preferred name:
NM_000548.3(TSC2):c.2714G>A (p.Arg905Gln)
HGVS:
  • NC_000016.10:g.2076142G>A
  • NG_005895.1:g.31837G>A
  • NM_000548.3:c.2714G>A
  • NP_000539.2:p.Arg905Gln
  • NC_000016.9:g.2126143G>A
  • p.(Arg905Gln)
Protein change:
R905Q; ARG905GLN
Links:
Tuberous sclerosis database (TSC2): TSC2_00134; OMIM: 191092.0013; dbSNP: 45517259
NCBI 1000 Genomes Browser:
rs45517259
Molecular consequence:
  • NM_000548.3:c.2714G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Tuberous sclerosis 2 (TSC2)
Identifiers:
MedGen: C1860707; Orphanet: 805; OMIM: 613254
Age of onset:
Childhood
Prevalence:
1-9 / 100 000 805

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Assertion and evidence details

Submission AccessionSubmitterReview StatusClinical Significance
(Last evaluated)
OriginMethodConsequenceCitations
SCV000033459OMIMPathogenic
(Aug 16, 2013)
germlineliterature only

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

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

Citations

PubMed

Unusually mild tuberous sclerosis phenotype is associated with TSC2 R905Q mutation.

Jansen AC, Sancak O, D'Agostino MD, Badhwar A, Roberts P, Gobbi G, Wilkinson R, Melanson D, Tampieri D, Koenekoop R, Gans M, Maat-Kievit A, Goedbloed M, van den Ouweland AM, Nellist M, Pandolfo M, McQueen M, Sims K, Thiele EA, Dubeau F, Andermann F, Kwiatkowski DJ, et al.

Ann Neurol. 2006 Nov;60(5):528-39.

PubMed [citation]
PMID:
17120248

Details of each submission

From OMIM, SCV000033459.1

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

Description

In affected members of a large French Canadian family with tuberous sclerosis (613254), Jansen et al. (2006) identified a heterozygous 2714G-A transition in exon 23 of the TSC2 gene, resulting in an arg905-to-gln (R905Q) substitution. The clinical phenotype was relatively mild in all affected individuals. There was complete absence of disfiguring skin lesions, radiographic apparent cortical tubers, intractable epilepsy, mental retardation, and severe organ involvement. Of 25 mutation carriers, 12 had a complete workup: 5 had definite TSC, 4 had probable TSC, 1 had possible TSC, and 2 fulfilled no diagnostic criteria for the disorder. Hypomelanotic macules were present in 92%, epilepsy in 60%, learning difficulties in 52%, imaging abnormalities in 24%, renal lesions in 8%, and retinal abnormalities in 4%. Additional studies identified 15 individuals from 5 families with the R905Q mutation. The phenotype was again relatively mild, similar to the first family. Of note, the mutation was not present in 1 family member with epilepsy and cognitive impairment nor in 5 family members with depigmented skin lesions. Jansen et al. (2006) referred to these cases as phenocopies.

Jansen et al. (2006) identified additional mutations in the same codon, R905W (191092.0014) and R905G (191092.0015), in patients with a more severe phenotype.

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

Last Updated: Feb 26, 2015