NM_022173.4(TIA1):c.209A>T (p.Lys70Met) AND Welander distal myopathy

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 28, 2019
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:: RCV001046830.7

Allele description [Variation Report for NM_022173.4(TIA1):c.209A>T (p.Lys70Met)]

NM_022173.4(TIA1):c.209A>T (p.Lys70Met)

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.209A>T (p.Lys70Met)

HGVS:

NC_000002.12:g.70230769T>A
NG_029967.1:g.22879A>T
NM_001351508.2:c.209A>T
NM_001351509.2:c.215A>T
NM_001351510.2:c.209A>T
NM_001351511.1:c.98A>T
NM_001351512.1:c.104A>T
NM_001351513.1:c.98A>T
NM_001351514.2:c.14A>T
NM_001351515.2:c.-181A>T
NM_001351516.2:c.209A>T
NM_001351517.2:c.-430A>T
NM_001351518.2:c.209A>T
NM_001351519.2:c.209A>T
NM_001351520.2:c.215A>T
NM_001351521.2:c.209A>T
NM_001351522.2:c.209A>T
NM_001351523.2:c.14A>T
NM_001351524.2:c.-207A>T
NM_001351525.2:c.-245A>T
NM_022037.4:c.209A>T
NM_022173.4:c.209A>TMANE SELECT
NP_001338437.1:p.Lys70Met
NP_001338438.1:p.Lys72Met
NP_001338439.1:p.Lys70Met
NP_001338440.1:p.Lys33Met
NP_001338441.1:p.Lys35Met
NP_001338442.1:p.Lys33Met
NP_001338443.1:p.Lys5Met
NP_001338445.1:p.Lys70Met
NP_001338447.1:p.Lys70Met
NP_001338448.1:p.Lys70Met
NP_001338449.1:p.Lys72Met
NP_001338450.1:p.Lys70Met
NP_001338451.1:p.Lys70Met
NP_001338452.1:p.Lys5Met
NP_071320.2:p.Lys70Met
NP_071505.2:p.Lys70Met
NC_000002.11:g.70457901T>A
NM_022173.2:c.209A>T
NR_147216.1:n.314A>T
NR_147217.1:n.314A>T
NR_147218.1:n.314A>T
NR_147219.2:n.407A>T
NR_147220.2:n.407A>T
NR_147221.2:n.407A>T
NR_147222.2:n.407A>T
NR_147223.2:n.407A>T
NR_147224.2:n.407A>T
NR_147225.2:n.407A>T
NR_147226.2:n.407A>T
NR_147227.2:n.407A>T
NR_147228.2:n.407A>T
NR_147229.2:n.407A>T
NR_147230.2:n.407A>T
NR_147231.2:n.407A>T
NR_147232.2:n.310A>T

Protein change:

K33M

Links:

dbSNP: rs1685916767

NCBI 1000 Genomes Browser:

rs1685916767

Molecular consequence:

NM_001351515.2:c.-181A>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001351517.2:c.-430A>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001351524.2:c.-207A>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001351525.2:c.-245A>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001351508.2:c.209A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001351509.2:c.215A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001351510.2:c.209A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001351511.1:c.98A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001351512.1:c.104A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001351513.1:c.98A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001351514.2:c.14A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001351516.2:c.209A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001351518.2:c.209A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001351519.2:c.209A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001351520.2:c.215A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001351521.2:c.209A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001351522.2:c.209A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001351523.2:c.14A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_022037.4:c.209A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_022173.4:c.209A>T - missense variant - [Sequence Ontology: SO:0001583]
NR_147216.1:n.314A>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_147217.1:n.314A>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_147218.1:n.314A>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_147219.2:n.407A>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_147220.2:n.407A>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_147221.2:n.407A>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_147222.2:n.407A>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_147223.2:n.407A>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_147224.2:n.407A>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_147225.2:n.407A>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_147226.2:n.407A>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_147227.2:n.407A>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_147228.2:n.407A>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_147229.2:n.407A>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_147230.2:n.407A>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_147231.2:n.407A>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_147232.2:n.310A>T - 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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SRP047252 (36)
SRA
hypothetical protein Syn7803C36_46 [Synechococcus phage ACG-2014b]
hypothetical protein Syn7803C36_46 [Synechococcus phage ACG-2014b]
gi|723042446|gb|AIX46101.1|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001210748	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 28, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001210748

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 28, 2019)

germline

clinical testing

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

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

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, SCV001210748.5

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

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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C15"). This variant has not been reported in the literature in individuals with TIA1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces lysine with methionine at codon 70 of the TIA1 protein (p.Lys70Met). The lysine residue is highly conserved and there is a moderate physicochemical difference between lysine and methionine.

#	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: Feb 28, 2024

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