NM_022173.4(TIA1):c.880G>A (p.Val294Met) AND Welander distal myopathy

Clinical significance:Uncertain significance (Last evaluated: Apr 27, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000697567.1

Allele description [Variation Report for NM_022173.4(TIA1):c.880G>A (p.Val294Met)]

NM_022173.4(TIA1):c.880G>A (p.Val294Met)

Gene:
TIA1:TIA1 cytotoxic granule associated RNA binding protein [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2p13.3
Genomic location:
Preferred name:
NM_022173.4(TIA1):c.880G>A (p.Val294Met)
HGVS:
  • NC_000002.12:g.70215379C>T
  • NG_029967.1:g.38269G>A
  • NM_001351508.2:c.880G>A
  • NM_001351509.2:c.853G>A
  • NM_001351510.2:c.847G>A
  • NM_001351511.1:c.769G>A
  • NM_001351512.1:c.742G>A
  • NM_001351513.1:c.736G>A
  • NM_001351514.2:c.652G>A
  • NM_001351515.2:c.577G>A
  • NM_001351517.2:c.460G>A
  • NM_001351524.2:c.460G>A
  • NM_001351525.2:c.460G>A
  • NM_022037.4:c.847G>A
  • NM_022173.4:c.880G>AMANE SELECT
  • NP_001338437.1:p.Val294Met
  • NP_001338438.1:p.Val285Met
  • NP_001338439.1:p.Val283Met
  • NP_001338440.1:p.Val257Met
  • NP_001338441.1:p.Val248Met
  • NP_001338442.1:p.Val246Met
  • NP_001338443.1:p.Val218Met
  • NP_001338444.1:p.Val193Met
  • NP_001338446.1:p.Val154Met
  • NP_001338453.1:p.Val154Met
  • NP_001338454.1:p.Val154Met
  • NP_071320.2:p.Val283Met
  • NP_071505.2:p.Val294Met
  • NC_000002.11:g.70442511C>T
  • NM_022173.2:c.880G>A
  • NR_147216.1:n.1237G>A
  • NR_147217.1:n.1118G>A
  • NR_147218.1:n.1118G>A
  • NR_147219.2:n.1078G>A
  • NR_147220.2:n.1173G>A
  • NR_147221.2:n.1244G>A
  • NR_147222.2:n.1239G>A
  • NR_147223.2:n.1297G>A
  • NR_147224.2:n.1178G>A
  • NR_147225.2:n.1330G>A
  • NR_147226.2:n.1178G>A
  • NR_147227.2:n.1139G>A
  • NR_147228.2:n.1211G>A
  • NR_147229.2:n.1045G>A
  • NR_147230.2:n.1396G>A
  • NR_147231.2:n.1211G>A
  • NR_147232.2:n.1081G>A
Protein change:
V154M
Links:
dbSNP: rs144296151
NCBI 1000 Genomes Browser:
rs144296151
Molecular consequence:
  • NM_001351508.2:c.880G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001351509.2:c.853G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001351510.2:c.847G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001351511.1:c.769G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001351512.1:c.742G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001351513.1:c.736G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001351514.2:c.652G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001351515.2:c.577G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001351517.2:c.460G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001351524.2:c.460G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001351525.2:c.460G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_022037.4:c.847G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_022173.4:c.880G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_147216.1:n.1237G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_147217.1:n.1118G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_147218.1:n.1118G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_147219.2:n.1078G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_147220.2:n.1173G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_147221.2:n.1244G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_147222.2:n.1239G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_147223.2:n.1297G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_147224.2:n.1178G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_147225.2:n.1330G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_147226.2:n.1178G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_147227.2:n.1139G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_147228.2:n.1211G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_147229.2:n.1045G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_147230.2:n.1396G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_147231.2:n.1211G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_147232.2:n.1081G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Welander distal myopathy (WDM)
Synonyms:
MUSCULAR DYSTROPHY, DISTAL, LATE-ONSET, AUTOSOMAL DOMINANT; Gower's muscular dystrophy; Welander distal myopathy, Swedish type; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0011466; MedGen: C0221054; Orphanet: 603; OMIM: 604454

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000826186Invitaecriteria provided, single submitter
Uncertain significance
(Apr 27, 2018)
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

TIA1 Mutations in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia Promote Phase Separation and Alter Stress Granule Dynamics.

Mackenzie IR, Nicholson AM, Sarkar M, Messing J, Purice MD, Pottier C, Annu K, Baker M, Perkerson RB, Kurti A, Matchett BJ, Mittag T, Temirov J, Hsiung GR, Krieger C, Murray ME, Kato M, Fryer JD, Petrucelli L, Zinman L, Weintraub S, Mesulam M, et al.

Neuron. 2017 Aug 16;95(4):808-816.e9. doi: 10.1016/j.neuron.2017.07.025.

PubMed [citation]
PMID:
28817800
PMCID:
PMC5576574

Clinical and neuropathological features of ALS/FTD with TIA1 mutations.

Hirsch-Reinshagen V, Pottier C, Nicholson AM, Baker M, Hsiung GR, Krieger C, Sengdy P, Boylan KB, Dickson DW, Mesulam M, Weintraub S, Bigio E, Zinman L, Keith J, Rogaeva E, Zivkovic SA, Lacomis D, Taylor JP, Rademakers R, Mackenzie IRA.

Acta Neuropathol Commun. 2017 Dec 7;5(1):96. doi: 10.1186/s40478-017-0493-x.

PubMed [citation]
PMID:
29216908
PMCID:
PMC5719900
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV000826186.1

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

Description

This sequence change replaces valine with methionine at codon 294 of the TIA1 protein (p.Val294Met). The valine residue is moderately conserved and there is a small physicochemical difference between valine and methionine. This variant is present in population databases (rs144296151, ExAC 0.02%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has been observed in an individual affected with amyotrophic lateral sclerosis (ALS) (PMID: 28817800, 29216908). 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. 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jul 27, 2020

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