NM_014845.6(FIG4):c.50T>C (p.Leu17Pro) AND Charcot-Marie-Tooth disease type 4

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 24, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV000697297.6

Allele description

NM_014845.6(FIG4):c.50T>C (p.Leu17Pro)

Gene:

FIG4:FIG4 phosphoinositide 5-phosphatase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6q21

Genomic location:

Preferred name:

NM_014845.6(FIG4):c.50T>C (p.Leu17Pro)

HGVS:

NC_000006.12:g.109691485T>C
NG_007977.1:g.5265T>C
NM_014845.6:c.50T>CMANE SELECT
NP_055660.1:p.Leu17Pro
NP_055660.1:p.Leu17Pro
LRG_241t1:c.50T>C
LRG_241:g.5265T>C
LRG_241p1:p.Leu17Pro
NC_000006.11:g.110012688T>C
NM_014845.5:c.50T>C
Q92562:p.Leu17Pro

Protein change:

L17P; LEU17PRO

Links:

UniProtKB: Q92562#VAR_071957; OMIM: 609390.0013; dbSNP: rs587777713

NCBI 1000 Genomes Browser:

rs587777713

Molecular consequence:

NM_014845.6:c.50T>C - missense variant - [Sequence Ontology: SO:0001583]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000825897	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Apr 24, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 21705420, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000825897

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Apr 24, 2023)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV000825897.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 17 of the FIG4 protein (p.Leu17Pro). 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 156014). This missense change has been observed in individual(s) with Charcot-Marie-Tooth (CMT) type-4J (PMID: 21705420). This variant is present in population databases (no rsID available, gnomAD 0.007%).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 16, 2024

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