VCV002019552.2 - ClinVar

NM_022173.4(TIA1):c.1100dup (p.Asn367fs)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(1)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Uncertain significance

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_022173.4(TIA1):c.1100dup (p.Asn367fs)

Variation ID: 2019552 Accession: VCV002019552.2

Type and length

Duplication, 1 bp

Location

Cytogenetic: 2p13.3 2: 70212779-70212780 (GRCh38) [ NCBI UCSC ] 2: 70439911-70439912 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Feb 8, 2023	Feb 20, 2024	Jul 25, 2022

HGVS

Nucleotide	Protein	Molecular consequence
NM_022173.4:c.1100dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_071505.2:p.Asn367fs	frameshift
NM_001351508.2:c.1097dup	NP_001338437.1:p.Asn366fs	frameshift
NM_001351509.2:c.1073dup	NP_001338438.1:p.Asn358fs	frameshift
NM_001351510.2:c.1064dup	NP_001338439.1:p.Asn355fs	frameshift
NM_001351511.1:c.989dup	NP_001338440.1:p.Asn330fs	frameshift
NM_001351512.1:c.962dup	NP_001338441.1:p.Asn321fs	frameshift
NM_001351513.1:c.956dup	NP_001338442.1:p.Asn319fs	frameshift
NM_001351514.2:c.872dup	NP_001338443.1:p.Asn291fs	frameshift
NM_001351515.2:c.797dup	NP_001338444.1:p.Asn266fs	frameshift
NM_001351517.2:c.677dup	NP_001338446.1:p.Asn226fs	frameshift
NM_001351524.2:c.680dup	NP_001338453.1:p.Asn227fs	frameshift
NM_001351525.2:c.680dup	NP_001338454.1:p.Asn227fs	frameshift
NM_022037.4:c.1067dup	NP_071320.2:p.Asn356fs	frameshift
NR_147216.1:n.1457dup		non-coding transcript variant
NR_147217.1:n.1338dup		non-coding transcript variant
NR_147218.1:n.1335dup		non-coding transcript variant
NR_147219.2:n.1407dup		non-coding transcript variant
NR_147220.2:n.1393dup		non-coding transcript variant
NR_147221.2:n.1464dup		non-coding transcript variant
NR_147222.2:n.1459dup		non-coding transcript variant
NR_147223.2:n.1517dup		non-coding transcript variant
NR_147224.2:n.1395dup		non-coding transcript variant
NR_147225.2:n.1550dup		non-coding transcript variant
NR_147226.2:n.1398dup		non-coding transcript variant
NR_147227.2:n.1468dup		non-coding transcript variant
NR_147228.2:n.1431dup		non-coding transcript variant
NR_147229.2:n.1374dup		non-coding transcript variant
NR_147230.2:n.1616dup		non-coding transcript variant
NR_147231.2:n.1428dup		non-coding transcript variant
NR_147232.2:n.1301dup		non-coding transcript variant
NC_000002.12:g.70212783dup
NC_000002.11:g.70439915dup
NG_029967.1:g.40868dup

... more HGVS ... less HGVS

Protein change

N226fs, N319fs, N367fs, N330fs, N355fs, N358fs, N366fs, N266fs, N321fs, N227fs, N291fs, N356fs

Other names

Canonical SPDI

NC_000002.12:70212779:TTTT:TTTTT

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
TIA1		-	-	GRCh38 GRCh37	283	296

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Welander distal myopathy	Uncertain significance (1)	criteria provided, single submitter	Jul 25, 2022	RCV002847189.3

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Uncertain significance (Jul 25, 2022)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Welander distal myopathy Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV003224666.2 First in ClinVar: Feb 07, 2023 Last updated: Feb 20, 2024	Comment: This sequence change creates a premature translational stop signal (p.Asn367Lysfs18) in the TIA1 gene. While this is not anticipated to result in nonsense mediated decay, … (more) This sequence change creates a premature translational stop signal (p.Asn367Lysfs18) in the TIA1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 20 amino acid(s) of the TIA1 protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TIA1-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. (less)

Comment:

This sequence change creates a premature translational stop signal (p.Asn367Lysfs*18) in the TIA1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 20 amino acid(s) of the TIA1 protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TIA1-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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.

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for this variant ...

Record last updated Sep 29, 2024

ClinVar Genomic variation as it relates to human health

NM_022173.4(TIA1):c.1100dup (p.Asn367fs)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...