NM_012470.4(TNPO3):c.2453G>A (p.Arg818Gln) AND Autosomal dominant limb-girdle muscular dystrophy type 1F

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 1, 2022
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:: RCV003062142.3

Allele description [Variation Report for NM_012470.4(TNPO3):c.2453G>A (p.Arg818Gln)]

NM_012470.4(TNPO3):c.2453G>A (p.Arg818Gln)

Gene:

TNPO3:transportin 3 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7q32.1

Genomic location:

Preferred name:

NM_012470.4(TNPO3):c.2453G>A (p.Arg818Gln)

HGVS:

NC_000007.14:g.128970293C>T
NG_023428.1:g.89881G>A
NM_001191028.3:c.2261G>A
NM_001382216.1:c.2555G>A
NM_001382217.1:c.2534G>A
NM_001382218.1:c.2453G>A
NM_001382219.1:c.2345G>A
NM_001382220.1:c.2312G>A
NM_001382221.1:c.2309G>A
NM_001382222.1:c.2306G>A
NM_001382223.1:c.2261G>A
NM_012470.4:c.2453G>AMANE SELECT
NP_001177957.2:p.Arg754Gln
NP_001369145.1:p.Arg852Gln
NP_001369146.1:p.Arg845Gln
NP_001369147.1:p.Arg818Gln
NP_001369148.1:p.Arg782Gln
NP_001369149.1:p.Arg771Gln
NP_001369150.1:p.Arg770Gln
NP_001369151.1:p.Arg769Gln
NP_001369152.1:p.Arg754Gln
NP_036602.1:p.Arg818Gln
NC_000007.13:g.128610347C>T
NR_034053.3:n.2955G>A
NR_167911.1:n.3042G>A
NR_167912.1:n.2900G>A
NR_167913.1:n.2702G>A
NR_167914.1:n.2862G>A
NR_167915.1:n.3118G>A
NR_167916.1:n.2592G>A
NR_167917.1:n.2625G>A
NR_167918.1:n.3080G>A
NR_167919.1:n.2919G>A
NR_167920.1:n.2878G>A
NR_167921.1:n.3080G>A
NR_167922.1:n.2916G>A
NR_167923.1:n.2717G>A
NR_167924.1:n.2794G>A
NR_167925.1:n.2717G>A
NR_167926.1:n.2728G>A
NR_167927.1:n.3021G>A

Protein change:

R754Q

Molecular consequence:

NM_001191028.3:c.2261G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001382216.1:c.2555G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001382217.1:c.2534G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001382218.1:c.2453G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001382219.1:c.2345G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001382220.1:c.2312G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001382221.1:c.2309G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001382222.1:c.2306G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001382223.1:c.2261G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_012470.4:c.2453G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_034053.3:n.2955G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_167911.1:n.3042G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_167912.1:n.2900G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_167913.1:n.2702G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_167914.1:n.2862G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_167915.1:n.3118G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_167916.1:n.2592G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_167917.1:n.2625G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_167918.1:n.3080G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_167919.1:n.2919G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_167920.1:n.2878G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_167921.1:n.3080G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_167922.1:n.2916G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_167923.1:n.2717G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_167924.1:n.2794G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_167925.1:n.2717G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_167926.1:n.2728G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_167927.1:n.3021G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Autosomal dominant limb-girdle muscular dystrophy type 1F (LGMDD2)
Synonyms:: Limb-girdle muscular dystrophy, type 1F; MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL DOMINANT 2
Identifiers:: MONDO: MONDO:0012034; MedGen: C1842062; Orphanet: 55595; OMIM: 608423

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003440172	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 1, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 30567601, 23667635, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003440172

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 1, 2022)

germline

clinical testing

PubMed (3)
[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

Long term follow-up and further molecular and histopathological studies in the LGMD1F sporadic TNPO3-mutated patient.

Gibertini S, Ruggieri A, Saredi S, Salerno F, Blasevich F, Napoli L, Moggio M, Nigro V, Morandi L, Maggi L, Mora M.

Acta Neuropathol Commun. 2018 Dec 19;6(1):141. doi: 10.1186/s40478-018-0648-4. No abstract available.

PubMed [citation]

PMID:: 30567601
PMCID:: PMC6299540

Next-generation sequencing identifies transportin 3 as the causative gene for LGMD1F.

Torella A, Fanin M, Mutarelli M, Peterle E, Del Vecchio Blanco F, Rispoli R, Savarese M, Garofalo A, Piluso G, Morandi L, Ricci G, Siciliano G, Angelini C, Nigro V.

PLoS One. 2013 May 7;8(5):e63536. doi: 10.1371/journal.pone.0063536. Print 2013.

PubMed [citation]

PMID:: 23667635
PMCID:: PMC3646821

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003440172.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

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. Experimental studies have shown that this missense change does not substantially affect TNPO3 function (PMID: 30567601). 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This missense change has been observed in individual(s) with limb-girdle muscular dystrophy (PMID: 23667635). This variant is present in population databases (rs587777431, gnomAD 0.02%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 818 of the TNPO3 protein (p.Arg818Gln).

#	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

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