NM_021629.4(GNB4):c.265A>C (p.Lys89Gln) AND Charcot-Marie-Tooth disease, dominant intermediate F

Clinical significance:Uncertain significance (Last evaluated: Sep 17, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001298055.1

Allele description [Variation Report for NM_021629.4(GNB4):c.265A>C (p.Lys89Gln)]

NM_021629.4(GNB4):c.265A>C (p.Lys89Gln)

Gene:
GNB4:G protein subunit beta 4 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
3q26.33
Genomic location:
Preferred name:
NM_021629.4(GNB4):c.265A>C (p.Lys89Gln)
HGVS:
  • NC_000003.12:g.179416495T>G
  • NG_033163.1:g.40089A>C
  • NM_021629.4:c.265A>CMANE SELECT
  • NP_067642.1:p.Lys89Gln
  • NC_000003.11:g.179134283T>G
Protein change:
K89Q
Molecular consequence:
  • NM_021629.4:c.265A>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Charcot-Marie-Tooth disease, dominant intermediate F (CMTDIF)
Identifiers:
MONDO: MONDO:0014074; MedGen: C3554654; Orphanet: 352670; OMIM: 615185

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001487096Invitaecriteria provided, single submitter
Uncertain significance
(Sep 17, 2020)
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

Exome sequencing identifies GNB4 mutations as a cause of dominant intermediate Charcot-Marie-Tooth disease.

Soong BW, Huang YH, Tsai PC, Huang CC, Pan HC, Lu YC, Chien HJ, Liu TT, Chang MH, Lin KP, Tu PH, Kao LS, Lee YC.

Am J Hum Genet. 2013 Mar 7;92(3):422-30. doi: 10.1016/j.ajhg.2013.01.014. Epub 2013 Feb 21.

PubMed [citation]
PMID:
23434117
PMCID:
PMC3591844

Mutation spectrum of Charcot-Marie-Tooth disease among the Han Chinese in Taiwan.

Hsu YH, Lin KP, Guo YC, Tsai YS, Liao YC, Lee YC.

Ann Clin Transl Neurol. 2019 Jun;6(6):1090-1101. doi: 10.1002/acn3.50797.

PubMed [citation]
PMID:
31211173
PMCID:
PMC6562034
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV001487096.1

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

Description

This sequence change replaces lysine with glutamine at codon 89 of the GNB4 protein (p.Lys89Gln). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and glutamine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with GNB4-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Benign; Align-GVGD: Class C0). This variant disrupts the p.Lys89 amino acid residue in GNB4. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 23434117, 31211173). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Jun 14, 2021

Support Center