NM_001370298.3(FGD4):c.1234C>T (p.Arg412Ter) AND Charcot-Marie-Tooth disease type 4

Clinical significance:Pathogenic (Last evaluated: Nov 6, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001248027.2

Allele description [Variation Report for NM_001370298.3(FGD4):c.1234C>T (p.Arg412Ter)]

NM_001370298.3(FGD4):c.1234C>T (p.Arg412Ter)

Gene:
FGD4:FYVE, RhoGEF and PH domain containing 4 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
12p11.21
Genomic location:
Preferred name:
NM_001370298.3(FGD4):c.1234C>T (p.Arg412Ter)
HGVS:
  • NC_000012.12:g.32601410C>T
  • NG_008626.2:g.206882C>T
  • NM_001304481.1:c.1078C>T
  • NM_001304483.2:c.79C>T
  • NM_001304484.2:c.-229C>T
  • NM_001330373.2:c.544C>T
  • NM_001330374.2:c.544C>T
  • NM_001370297.1:c.271C>T
  • NM_001370298.3:c.1234C>TMANE SELECT
  • NM_001384126.1:c.1234C>T
  • NM_001384127.1:c.823C>T
  • NM_001384128.1:c.823C>T
  • NM_001384130.1:c.544C>T
  • NM_001385118.1:c.823C>T
  • NM_139241.3:c.823C>T
  • NP_001291410.1:p.Arg360Ter
  • NP_001291412.1:p.Arg27Ter
  • NP_001317302.1:p.Arg182Ter
  • NP_001317303.1:p.Arg182Ter
  • NP_001357226.1:p.Arg91Ter
  • NP_001357227.2:p.Arg412Ter
  • NP_001371055.1:p.Arg412Ter
  • NP_001371056.1:p.Arg275Ter
  • NP_001371057.1:p.Arg275Ter
  • NP_001371059.1:p.Arg182Ter
  • NP_001372047.1:p.Arg275Ter
  • NP_640334.2:p.Arg275Ter
  • LRG_240t1:c.823C>T
  • LRG_240t2:c.1078C>T
  • LRG_240:g.206882C>T
  • LRG_240p1:p.Arg275Ter
  • LRG_240p2:p.Arg360Ter
  • NC_000012.11:g.32754344C>T
  • NM_139241.2:c.823C>T
Protein change:
R182*; ARG275TER
Links:
OMIM: 611104.0006; dbSNP: rs118203974
NCBI 1000 Genomes Browser:
rs118203974
Molecular consequence:
  • NM_001304484.2:c.-229C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001304481.1:c.1078C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001304483.2:c.79C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001330373.2:c.544C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001330374.2:c.544C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001370297.1:c.271C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001370298.3:c.1234C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001384126.1:c.1234C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001384127.1:c.823C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001384128.1:c.823C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001384130.1:c.544C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001385118.1:c.823C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_139241.3:c.823C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Charcot-Marie-Tooth disease type 4
Synonyms:
Charcot-Marie-Tooth, Type 4
Identifiers:
MONDO: MONDO:0018995; MedGen: C4082197

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001421486Invitaecriteria provided, single submitter
Pathogenic
(Nov 6, 2019)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

A novel Frabin (FGD4) nonsense mutation p.R275X associated with phenotypic variability in CMT4H.

Houlden H, Hammans S, Katifi H, Reilly MM.

Neurology. 2009 Feb 17;72(7):617-20. doi: 10.1212/01.wnl.0000342463.35089.cc.

PubMed [citation]
PMID:
19221294
PMCID:
PMC2677538

Peripheral nerve demyelination caused by a mutant Rho GTPase guanine nucleotide exchange factor, frabin/FGD4.

Stendel C, Roos A, Deconinck T, Pereira J, Castagner F, Niemann A, Kirschner J, Korinthenberg R, Ketelsen UP, Battaloglu E, Parman Y, Nicholson G, Ouvrier R, Seeger J, De Jonghe P, Weis J, Krüttgen A, Rudnik-Schöneborn S, Bergmann C, Suter U, Zerres K, Timmerman V, et al.

Am J Hum Genet. 2007 Jul;81(1):158-64. Epub 2007 May 24.

PubMed [citation]
PMID:
17564972
PMCID:
PMC1950925
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV001421486.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change creates a premature translational stop signal (p.Arg275*) in the FGD4 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs118203974, ExAC 0.006%). This variant has been observed in individual(s) with Charcot-Marie-Tooth disease (PMID: 19221294). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 1016). Loss-of-function variants in FGD4 are known to be pathogenic (PMID: 17564972). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Oct 30, 2021

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