VCV000598745.5 - ClinVar

NM_014604.4(TAX1BP3):c.233T>C (p.Met78Thr)

Germline

Classification

criteria provided, conflicting classifications. Learn more about how ClinVar calculates review status.

Conflicting classifications of pathogenicity
Likely pathogenic(1); Uncertain significance(1)

2 out of 2 submissions contributed to this 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.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_014604.4(TAX1BP3):c.233T>C (p.Met78Thr)

Variation ID: 598745 Accession: VCV000598745.5

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 17p13.2 17: 3664199 (GRCh38) [ NCBI UCSC ] 17: 3567493 (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	Dec 16, 2018	Apr 13, 2025	Apr 16, 2020

HGVS

Nucleotide	Protein	Molecular consequence
NM_014604.4:c.233T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_055419.1:p.Met78Thr	missense
NM_001204698.2:c.160-314T>C		intron variant
NR_037928.1:n.5288T>C		non-coding transcript variant
NC_000017.11:g.3664199A>G
NC_000017.10:g.3567493A>G
NG_012489.2:g.32732A>G
NG_053154.1:g.9481T>C

... more HGVS ... less HGVS

Protein change

M78T

Other names

Canonical SPDI

NC_000017.11:3664198:A:G

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

ClinGen: CA397696100 dbSNP: rs1307997067 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.
P2RX5-TAX1BP3	-	-	-	GRCh38	-	153
TAX1BP3		-	-	GRCh38 GRCh37	-	103

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.
TAX1BP3-related arrhythmogenic right ventricular cardiomyopathy	Likely pathogenic (1)	criteria provided, single submitter	Nov 27, 2018	RCV000735208.3
Primary familial dilated cardiomyopathy	Uncertain significance (1)	criteria provided, single submitter	Apr 16, 2020	RCV001195116.1

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.	Expand all rows Collapse all rows 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 (Apr 16, 2020) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Primary familial dilated cardiomyopathy	Department of Molecular and Human Genetics, Baylor College of Medicine Accession: SCV001334127.1 First in ClinVar: Jul 04, 2020 Last updated: Jul 04, 2020	Publications: PubMed (2) PubMed: 32576985‚ 25645515 Observation: 1 Collection method: clinical testing Allele origin: inherited Affected status: yes more Observation 1 Collection method: clinical testing Allele origin: inherited Affected status: yes Zygosity: Single Heterozygote Comment on evidence: 238 Kb deletion encompassing the entire TAX1BP3

Likely pathogenic (Nov 27, 2018) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	TAX1BP3-related arrhythmogenic right ventricular cardiomyopathy (Autosomal recessive inheritance)	Undiagnosed Diseases Network, NIH Accession: SCV000863415.2 First in ClinVar: Dec 16, 2018 Last updated: Apr 13, 2025	Comment: show A hemizygous c.233T>C (p.M78T) variant in the TAX1BP3 gene was detected in three brothers (14yo male, 20yo male, and male that died suddently at age 17) with similar symptoms. Exome sequencing showed that all three brothers are hemizygous, the mother is heterozygous, and the father is negative for this change. Concurrent array analysis revealed a heterozygous copy number loss of approximately 238 Kb in size (genomic position chr17:3394299- 3632836) in all three brothers. This large deletion encompasses the entire TAX1BP3 gene. SNP arrays detected this deletion as heterozygous in all three brothers and the father. The mother is negative for the deletion. Therefore, the 238 Kb deletion and the c.233T>C (p.M78T) variant are located on two chromosomes (in trans configuration). We believe the combination of the missense variant and deletion in trans is likely pathogenic. (less) Observation: 2 Observation 1 Collection method: clinical testing Allele origin: maternal Affected status: yes Number of individuals with the variant: 3 Number of families with the variant: 1 Clinical Features: Type I diabetes mellitus (present) , Tachycardia (present) , Speech apraxia (present) , Short philtrum (present) , Right ventricular cardiomyopathy (present) , Enuresis (present) , Attention deficit hyperactivity disorder (present) Zygosity: Compound Heterozygote Age: 14-20 years Sex: male Ethnicity/Population group: White Tissue: blood Platform type: exome sequencing Platform name: HiSeq Testing laboratory: Baylor Genetics Date variant was reported to submitter: 2018-06-22 Testing laboratory interpretation: Uncertain significance Observation 2 Collection method: clinical testing Allele origin: unknown Affected status: no Number of individuals with the variant: 1 Zygosity: Single Heterozygote Age: 40-49 years Sex: female Ethnicity/Population group: White Tissue: blood Platform Type: exome sequencing Platform Name: HiSeq Testing laboratory: Baylor Genetics Date variant was reported to submitter: 2018-06-22 Testing laboratory interpretation: Uncertain significance

Comment:

A hemizygous c.233T>C (p.M78T) variant in the TAX1BP3 gene was detected in three brothers (14yo male, 20yo male, and male that died suddently at age 17) with similar symptoms. Exome sequencing showed that all three brothers are hemizygous, the mother is heterozygous, and the father is negative for this change. Concurrent array analysis revealed a heterozygous copy number loss of approximately 238 Kb in size (genomic position chr17:3394299- 3632836) in all three brothers. This large deletion encompasses the entire TAX1BP3 gene. SNP arrays detected this deletion as heterozygous in all three brothers and the father. The mother is negative for the deletion. Therefore, the 238 Kb deletion and the c.233T>C (p.M78T) variant are located on two chromosomes (in trans configuration). We believe the combination of the missense variant and deletion in trans is likely pathogenic.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
CNVs cause autosomal recessive genetic diseases with or without involvement of SNV/indels.	Yuan B	Genetics in medicine : official journal of the American College of Medical Genetics	2020	PMID: 32576985
Mutations in TAX1BP3 cause dilated cardiomyopathy with septo-optic dysplasia.	Reinstein E	Human mutation	2015	PMID: 25645515

Text-mined citations for rs1307997067 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Oct 18, 2025

ClinVar Genomic variation as it relates to human health

NM_014604.4(TAX1BP3):c.233T>C (p.Met78Thr)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Citations for germline classification of this variant

Text-mined citations for rs1307997067 ...