Is TTN p.Arg34698Ter (c.104092C>T) pathogenic?

TTN p.Arg34698Ter (c.104092C>T) is classified Likely pathogenic in TTN (ClinVar, Multiple submitters, 8 submitters; last evaluated 2025-08-04). Very rare (popmax 0.00134%, afr); Associated with autosomal recessive limb-girdle muscular dystrophy type 2J.

How common is TTN p.Arg34698Ter (c.104092C>T) in the general population?

TTN p.Arg34698Ter (c.104092C>T) is very rare (popmax 0.00134%, afr) (gnomAD).

How is Titin-related limb-girdle muscular dystrophy R10 inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

TTN p.Arg34698Ter

Q: What condition is associated with TTN p.Arg34698Ter (c.104092C>T)?

TTN p.Arg34698Ter (c.104092C>T) is associated with autosomal recessive limb-girdle muscular dystrophy type 2J, dilated cardiomyopathy, tibial muscular dystrophy (ClinVar).

c.104092C>T · rs727504184 · VCV167754

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Conditions

autosomal recessive limb-girdle muscular dystrophy type 2J

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 358 of 363
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.8, phastCons 1
Overall
CADD	76.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,904 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000186% 3/1,613,838 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,904
European (non-Finnish)	0.00017%	589,932

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: TTN
Protein: p.Arg34698Ter
Coding: c.104092C>T
MANE Select: NM_001267550
dbSNP: rs727504184
Type: single nucleotide variant
Location: chr2:178532523 (GRCh38)
Gene constraint: LOEUF 0.479 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)

Full TTN gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autosomal recessive limb-girdle muscular dystrophy type 2J — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: dilated cardiomyopathy tibial muscular dystrophy myopathy, myofibrillar, 9, with early respiratory failure dilated cardiomyopathy 1G early-onset myopathy with fatal cardiomyopathy hypertrophic cardiomyopathy 9

For Titin-related limb-girdle muscular dystrophy R10 (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood

Similar variants

TTN p.Arg34698Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
TTN p.Arg34698= Likely benign ★ same residue
TTN p.Arg34698fs Likely pathogenic ★ same residue
TTN c.100171+1G>A Likely pathogenic ★★ same condition
TTN c.100766-1G>T Likely pathogenic ★★ same condition
TTN c.100766-2A>T Likely pathogenic ★★ same condition
TTN c.106375-2A>G Pathogenic/Likely pathogenic ★★ same condition
TTN c.106531+1G>A Pathogenic/Likely pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/ttn-p-arg34698ter (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown