NM_001136472.2(LITAF):c.385G>A (p.Ala129Thr) AND Charcot-Marie-Tooth disease type 1C

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Apr 16, 2021
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:: RCV000192669.16

Allele description [Variation Report for NM_001136472.2(LITAF):c.385G>A (p.Ala129Thr)]

NM_001136472.2(LITAF):c.385G>A (p.Ala129Thr)

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.385G>A (p.Ala129Thr)

HGVS:

NC_000016.10:g.11549738C>T
NG_009008.1:g.42213G>A
NM_001136472.2:c.385G>AMANE SELECT
NM_001136473.1:c.*24G>A
NM_004862.4:c.385G>A
NP_001129944.1:p.Ala129Thr
NP_004853.2:p.Ala129Thr
LRG_253t1:c.*24G>A
LRG_253:g.42213G>A
NC_000016.9:g.11643594C>T
NM_004862.3:c.385G>A
NR_024320.2:n.519G>A

Protein change:

A129T

Links:

dbSNP: rs797044847

NCBI 1000 Genomes Browser:

rs797044847

Molecular consequence:

NM_001136473.1:c.*24G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001136472.2:c.385G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_004862.4:c.385G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_024320.2:n.519G>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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000243951	GeneReviews	no classification provided	not provided	germline	literature only
SCV002186001	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Apr 16, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 24844793, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000243951

GeneReviews

no classification provided

not provided

germline

literature only

SCV002186001

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Apr 16, 2021)

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	yes	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A novel LITAF/SIMPLE variant within a family with minimal demyelinating Charcot-Marie-Tooth disease.

Luigetti M, Fabrizi GM, Taioli F, Del Grande A, Lo Monaco M.

Neurol Sci. 2014 Dec;35(12):2005-7. doi: 10.1007/s10072-014-1833-2. Epub 2014 May 21. No abstract available.

PubMed [citation]

PMID:: 24844793

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 GeneReviews, SCV000243951.2

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

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002186001.3

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

Description

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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been observed in individual(s) with clinical features of Charcot-Marie-Tooth disease (PMID: 24844793). ClinVar contains an entry for this variant (Variation ID: 208245). This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with threonine at codon 129 of the LITAF protein (p.Ala129Thr). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine 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: Nov 24, 2024

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