TVP23C-CDRT4

Chr 17

TVP23C-CDRT4 readthrough

Also known as: FAM18B2-CDRT4

This locus encodes a readthrough fusion protein that combines sequences from the trans-Golgi network vesicle protein TVP23C with CDRT4, though the specific function of this fusion protein remains unclear. Mutations cause autosomal recessive developmental and epileptic encephalopathy with microcephaly, typically presenting in early infancy with severe intellectual disability and refractory seizures. The gene shows very low constraint against loss-of-function variants, suggesting haploinsufficiency is likely tolerated.

ResearchSummary from RefSeq

This locus represents naturally occurring readthrough transcription between the neighboring TVP23C (trans-golgi network vesicle protein 23 homolog) and CDRT4 (CMT1A duplicated region transcript 4) genes on chromosome 17. Alternative splicing results in multiple transcript variants, one of which encodes a protein that shares sequence identity with the upstream gene product, but its C-terminus is distinct due to frameshifts relative to the downstream gene. [provided by RefSeq, Apr 2014]

ResearchGenerating clinical summary…

LOEUF 1.48

Clinical Summary— TVP23C-CDRT4

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

20 VUS of 26 total submissions

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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.48LOEUF

pLI 0.000

Z-score 0.38

OE 0.88 (0.54–1.48)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.06Z-score

OE missense 0.98 (0.82–1.18)

83 obs / 84.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.88 (0.54–1.48)

0≤0.351.4

Missense OE?0.98 (0.82–1.18)

0≤0.61.4

Synonymous OE?0.99

0≤1.21.6

LoF obs/exp: 10 / 11.4Missense obs/exp: 83 / 84.6Syn Z: 0.02

ClinVar Variant Classifications

26 submitted variants in ClinVar

ClinVar

Classification Summary

VUS20

Likely Benign6

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	20	0	20
Likely Benign	5	1	6
Benign	0	0	0
Total	25	1	26

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

121 pathogenic / likely-pathogenic (of 129) ClinVar copy-number / structural variants overlap TVP23C-CDRT4 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →