Is TTN p.Arg34110Pro (c.102329G>C) pathogenic?

TTN p.Arg34110Pro (c.102329G>C) is classified Uncertain significance in TTN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-11-03). AlphaMissense: likely pathogenic (0.9652); Absent from gnomAD v4.1; Associated with autosomal recessive limb-girdle muscular dystrophy type 2J.

How common is TTN p.Arg34110Pro (c.102329G>C) in the general population?

TTN p.Arg34110Pro (c.102329G>C) is absent from gnomAD v4.1 (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.

What do computational predictors say about TTN p.Arg34110Pro (c.102329G>C)?

AlphaMissense predicts likely pathogenic (score 0.9652) — an in-silico prediction, not a clinical call.

TTN p.Arg34110Pro

Q: What condition is associated with TTN p.Arg34110Pro (c.102329G>C)?

TTN p.Arg34110Pro (c.102329G>C) is associated with autosomal recessive limb-girdle muscular dystrophy type 2J, dilated cardiomyopathy 1G (ClinVar).

c.102329G>C · rs565347600 · VCV466701

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9652 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

autosomal recessive limb-girdle muscular dystrophy type 2J

Computational evidence

Protein change
AlphaMissense	0.9652	likely pathogenic
REVEL	0.529	indeterminate
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.7	GERP 2.8, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 75 kb · p 3.1e-23 · regional, not allelic
Overall
CADD	21.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R32469P vs ClinVar R34110P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TTN
Protein: p.Arg34110Pro
Coding: c.102329G>C
dbSNP: rs565347600
Type: single nucleotide variant
Location: chr2:178534286 (GRCh38)

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 1G

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

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood

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-arg34110pro (accessed [today's date]).

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