NM_014845.6(FIG4):c.1666dup (p.Thr556fs) AND Charcot-Marie-Tooth disease type 4

Clinical significance:Pathogenic (Last evaluated: Oct 10, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000798693.2

Allele description [Variation Report for NM_014845.6(FIG4):c.1666dup (p.Thr556fs)]

NM_014845.6(FIG4):c.1666dup (p.Thr556fs)

Gene:
FIG4:FIG4 phosphoinositide 5-phosphatase [Gene - OMIM - HGNC]
Variant type:
Duplication
Cytogenetic location:
6q21
Genomic location:
Preferred name:
NM_014845.6(FIG4):c.1666dup (p.Thr556fs)
HGVS:
  • NC_000006.12:g.109766811dup
  • NG_007977.1:g.80591dup
  • NM_014845.5:c.1666dup
  • NM_014845.6:c.1666dupMANE SELECT
  • NP_055660.1:p.Thr556fs
  • NP_055660.1:p.Thr556fs
  • LRG_241t1:c.1666dup
  • LRG_241:g.80591dup
  • LRG_241p1:p.Thr556fs
  • NC_000006.11:g.110088010_110088011insA
  • NC_000006.11:g.110088014dup
  • NM_014845.5:c.1666dupA
Protein change:
T556fs
Links:
dbSNP: rs772320287
NCBI 1000 Genomes Browser:
rs772320287
Molecular consequence:
  • NM_014845.5:c.1666dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_014845.6:c.1666dup - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV000938320Invitaecriteria provided, single submitter
Pathogenic
(Oct 10, 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

Distinctive genetic and clinical features of CMT4J: a severe neuropathy caused by mutations in the PI(3,5)P₂ phosphatase FIG4.

Nicholson G, Lenk GM, Reddel SW, Grant AE, Towne CF, Ferguson CJ, Simpson E, Scheuerle A, Yasick M, Hoffman S, Blouin R, Brandt C, Coppola G, Biesecker LG, Batish SD, Meisler MH.

Brain. 2011 Jul;134(Pt 7):1959-71. doi: 10.1093/brain/awr148.

PubMed [citation]
PMID:
21705420
PMCID:
PMC3122378

Yunis-Varón syndrome is caused by mutations in FIG4, encoding a phosphoinositide phosphatase.

Campeau PM, Lenk GM, Lu JT, Bae Y, Burrage L, Turnpenny P, Román Corona-Rivera J, Morandi L, Mora M, Reutter H, Vulto-van Silfhout AT, Faivre L, Haan E, Gibbs RA, Meisler MH, Lee BH.

Am J Hum Genet. 2013 May 2;92(5):781-91. doi: 10.1016/j.ajhg.2013.03.020. Epub 2013 Apr 25.

PubMed [citation]
PMID:
23623387
PMCID:
PMC3644641
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV000938320.3

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

Description

This sequence change creates a premature translational stop signal (p.Thr556Asnfs*21) in the FIG4 gene. It is expected to result in an absent or disrupted protein product. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been observed in individuals affected with autosomal recessive Charcot-Marie-Tooth disease (PMID: 21705420). ClinVar contains an entry for this variant (Variation ID: 355040). Loss-of-function variants in FIG4 are known to be pathogenic (PMID: 23623387). 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: Nov 27, 2021

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