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NM_018972.4(GDAP1):c.821C>T (p.Pro274Leu) AND Charcot-Marie-Tooth disease axonal type 2K

Germline classification:
Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:
Jan 6, 2016
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:
RCV000043550.6

Allele description [Variation Report for NM_018972.4(GDAP1):c.821C>T (p.Pro274Leu)]

NM_018972.4(GDAP1):c.821C>T (p.Pro274Leu)

Gene:
GDAP1:ganglioside induced differentiation associated protein 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
8q21.11
Genomic location:
Preferred name:
NM_018972.4(GDAP1):c.821C>T (p.Pro274Leu)
HGVS:
  • NC_000008.11:g.74364111C>T
  • NG_008787.3:g.47982C>T
  • NM_001040875.4:c.617C>T
  • NM_001362929.2:c.494C>T
  • NM_001362930.2:c.647C>T
  • NM_001362931.2:c.694+1058C>T
  • NM_001362932.2:c.494C>T
  • NM_018972.4:c.821C>TMANE SELECT
  • NP_001035808.1:p.Pro206Leu
  • NP_001349858.1:p.Pro165Leu
  • NP_001349859.1:p.Pro216Leu
  • NP_001349861.1:p.Pro165Leu
  • NP_061845.2:p.Pro274Leu
  • LRG_244t1:c.821C>T
  • LRG_244:g.47982C>T
  • NC_000008.10:g.75276346C>T
  • NM_018972.2:c.821C>T
Protein change:
P165L; PRO274LEU
Links:
OMIM: 606598.0019; dbSNP: rs397515443
NCBI 1000 Genomes Browser:
rs397515443
Molecular consequence:
  • NM_001362931.2:c.694+1058C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001040875.4:c.617C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001362929.2:c.494C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001362930.2:c.647C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001362932.2:c.494C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_018972.4:c.821C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Charcot-Marie-Tooth disease axonal type 2K
Synonyms:
CHARCOT-MARIE-TOOTH NEUROPATHY, AXONAL, TYPE 2K; Charcot-Marie-Tooth disease type 2K; Charcot-Marie-Tooth disease, axonal, autosomal recessive, Type 2K
Identifiers:
MONDO: MONDO:0011916; MedGen: C1842983; Orphanet: 99944; OMIM: 607831

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000071291OMIM
no assertion criteria provided
Pathogenic
(Aug 9, 2011) 		germlineliterature only

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

SCV004174615Inherited Neuropathy Consortium Ii, University Of Miami
no assertion criteria provided
Uncertain significance
(Jan 6, 2016) 		germlineliterature only

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

Help

Summary from all submissions

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

Citations

PubMed

Dominant GDAP1 mutations cause predominantly mild CMT phenotypes.

Zimoń M, Baets J, Fabrizi GM, Jaakkola E, Kabzińska D, Pilch J, Schindler AB, Cornblath DR, Fischbeck KH, Auer-Grumbach M, Guelly C, Huber N, De Vriendt E, Timmerman V, Suter U, Hausmanowa-Petrusewicz I, Niemann A, Kochański A, De Jonghe P, Jordanova A.

Neurology. 2011 Aug 9;77(6):540-8. doi: 10.1212/WNL.0b013e318228fc70. Epub 2011 Jul 13.

PubMed [citation]
PMID:
21753178
PMCID:
PMC3272385

Details of each submission

From OMIM, SCV000071291.3

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

Description

In an Italian father and son with autosomal dominant Charcot-Marie-Tooth disease type 2K (CMT2K; see 607831), Zimon et al. (2011) identified a heterozygous 821C-T transition in the GDAP1 gene, resulting in a pro274-to-leu (P274L) substitution at a highly conserved residue in the C-terminal GST domain. The mutation was not found in 280 control individuals. The father, who had onset of distal muscle weakness and atrophy at age 47 years and became wheelchair-bound at age 61, had an intermediate pattern on nerve conduction studies. The son was clinically asymptomatic, but showed an axonal pattern on nerve conduction studies.

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

From Inherited Neuropathy Consortium Ii, University Of Miami, SCV004174615.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Feb 4, 2024