Is TTN p.Arg26258= (c.78774A>G) pathogenic?

TTN p.Arg26258= (c.78774A>G) is classified Conflicting classifications of pathogenicity in TTN (ClinVar, Conflicting submitters, 9 submitters; last evaluated 2026-01-06). Very rare (popmax 0.00784%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with TTN p.Arg26258= (c.78774A>G)?

TTN p.Arg26258= (c.78774A>G) is associated with Cardiovascular phenotype, tibial muscular dystrophy, myopathy, myofibrillar, 9, with early respiratory failure (ClinVar).

How common is TTN p.Arg26258= (c.78774A>G) in the general population?

TTN p.Arg26258= (c.78774A>G) is very rare (popmax 0.00784%, nfe) (gnomAD).

TTN p.Arg26258=

c.78774A>G · rs368270588 · VCV178185

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00784%, nfe)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 1.6	GERP 1.8, phastCons 1
Overall
CADD	0.59	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00784% European (non-Finnish) · 92/1,173,342 alleles

Filtering AF 0.00651% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00604%

Overall 0.00595% 95/1,595,482 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00784%	12,754
Remaining individualsnot grpmax-eligible	0.00487%	20,533

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.Arg26258=
Coding: c.78774A>G
dbSNP: rs368270588
Type: single nucleotide variant
Location: chr2:178567358 (GRCh38)

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

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: tibial muscular dystrophy myopathy, myofibrillar, 9, with early respiratory failure dilated cardiomyopathy 1G autosomal recessive limb-girdle muscular dystrophy type 2J early-onset myopathy with fatal cardiomyopathy

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-arg26258 (accessed [today's date]).

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