Is TTN p.Arg34883Cys (c.104647C>T) pathogenic?

TTN p.Arg34883Cys (c.104647C>T) is classified Uncertain significance in TTN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-27). AlphaMissense: likely pathogenic (0.8744); Very rare (popmax 0.00223%, eas); Associated with dilated cardiomyopathy 1G.

What condition is associated with TTN p.Arg34883Cys (c.104647C>T)?

TTN p.Arg34883Cys (c.104647C>T) is associated with dilated cardiomyopathy 1G, autosomal recessive limb-girdle muscular dystrophy type 2J (ClinVar).

How common is TTN p.Arg34883Cys (c.104647C>T) in the general population?

TTN p.Arg34883Cys (c.104647C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

How is Familial isolated dilated cardiomyopathy inherited?

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

What do computational predictors say about TTN p.Arg34883Cys (c.104647C>T)?

AlphaMissense predicts likely pathogenic (score 0.8744) — an in-silico prediction, not a clinical call.

TTN p.Arg34883Cys

c.104647C>T · rs1003158162 · VCV1363285

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8744 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

dilated cardiomyopathy 1G

Computational evidence

Protein change
AlphaMissense	0.8744	likely pathogenic
REVEL	0.516	indeterminate
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 10	GERP 2.6, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 75 kb · p 3.1e-23 · regional, not allelic
Overall
CADD	23.4	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 R33242C vs ClinVar R34883C) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,840 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000479% 7/1,461,458 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,840
Admixed American	0.00167%	59,992
European (non-Finnish)	0.000424%	235,958

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.Arg34883Cys
Coding: c.104647C>T
dbSNP: rs1003158162
Type: single nucleotide variant
Location: chr2:178531968 (GRCh38)

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

Disease context

dilated cardiomyopathy 1G — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autosomal recessive limb-girdle muscular dystrophy type 2J

For Familial isolated dilated cardiomyopathy (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: All ages
Prevalence: 1-9 / 100 000 (Europe)

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-arg34883cys (accessed [today's date]).

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