NM_001136472.2(LITAF):c.403C>A (p.Pro135Thr) AND Charcot-Marie-Tooth disease type 1C

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Dec 25, 2020
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:: RCV000034129.10

Allele description [Variation Report for NM_001136472.2(LITAF):c.403C>A (p.Pro135Thr)]

NM_001136472.2(LITAF):c.403C>A (p.Pro135Thr)

Gene:

LITAF:lipopolysaccharide induced TNF factor [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16p13.13

Genomic location:

Preferred name:

NM_001136472.2(LITAF):c.403C>A (p.Pro135Thr)

HGVS:

NC_000016.10:g.11549720G>T
NG_009008.1:g.42231C>A
NM_001136472.2:c.403C>AMANE SELECT
NM_001136473.1:c.*42C>A
NM_004862.4:c.403C>A
NP_001129944.1:p.Pro135Thr
NP_004853.2:p.Pro135Thr
NP_004853.2:p.Pro135Thr
LRG_253t1:c.*42C>A
LRG_253:g.42231C>A
NC_000016.9:g.11643576G>T
NM_004862.3:c.403C>A
NR_024320.2:n.537C>A

Protein change:

P135T

Links:

dbSNP: rs281865135

NCBI 1000 Genomes Browser:

rs281865135

Molecular consequence:

NM_001136473.1:c.*42C>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001136472.2:c.403C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_004862.4:c.403C>A - missense variant - [Sequence Ontology: SO:0001583]
NR_024320.2:n.537C>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Charcot-Marie-Tooth disease type 1C
Synonyms:: CMT, SLOW NERVE CONDUCTION TYPE C; HMSN IC; CMT 1C; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010995; MedGen: C0270913; Orphanet: 101083; OMIM: 601098

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000058059	GeneReviews	no classification provided	not provided	unknown	literature only	PubMed (1) [See all records that cite this PMID]
SCV002236909	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 25, 2020)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 21896645, 25058650, 23166352, 16787513, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000058059

GeneReviews

no classification provided

not provided

unknown

literature only

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

SCV002236909

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 25, 2020)

germline

clinical testing

PubMed (5)
[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
not provided	unknown	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Charcot-Marie-Tooth Neuropathy Type 1 – RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY.

Bird TD.

1998 Aug 31 [updated 2015 Mar 26]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(®) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024.

PubMed [citation]

PMID:: 20301384

Mutations associated with Charcot-Marie-Tooth disease cause SIMPLE protein mislocalization and degradation by the proteasome and aggresome-autophagy pathways.

Lee SM, Olzmann JA, Chin LS, Li L.

J Cell Sci. 2011 Oct 1;124(Pt 19):3319-31. doi: 10.1242/jcs.087114. Epub 2011 Sep 6.

PubMed [citation]

PMID:: 21896645
PMCID:: PMC3178453

See all PubMed Citations (6)

Details of each submission

From GeneReviews, SCV000058059.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002236909.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this variant affects LITAF protein function (PMID: 21896645, 25058650, 23166352). This variant has been observed in individual(s) with Charcot-Marie-Tooth disease (PMID: 16787513). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 41230). This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with threonine at codon 135 of the LITAF protein (p.Pro135Thr). The proline residue is moderately conserved and there is a small physicochemical difference between proline and threonine.

#	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 29, 2024

ClinVar

Relating variation to medicine