Is TTN p.Val45= (c.135G>T) pathogenic?

TTN p.Val45= (c.135G>T) is classified Likely benign in TTN (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-23). Very rare (popmax 0.00169%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with TTN p.Val45= (c.135G>T)?

TTN p.Val45= (c.135G>T) is associated with Cardiovascular phenotype (ClinVar).

How common is TTN p.Val45= (c.135G>T) in the general population?

TTN p.Val45= (c.135G>T) is very rare (popmax 0.00169%, nfe) (gnomAD).

TTN p.Val45=

c.135G>T · rs1189066391 · VCV1770812

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00169%, nfe)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>T here scores Δ0.35 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.44	GERP -3.9, phastCons 0.015
Overall
CADD	7.493	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00169% European (non-Finnish) · 20/1,180,014 alleles

Filtering AF 0.00111% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0009%

Overall 0.00124% 20/1,614,000 alleles · very rare exomes 19/1,461,826 · genomes 1/152,174 · joint denominator

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.Val45=
Coding: c.135G>T
MANE Select: NM_001267550
dbSNP: rs1189066391
Type: single nucleotide variant
Location: chr2:178802298 (GRCh38)
Gene constraint: LOEUF 0.479 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
Residue 45: the ig-like 1 domain; a β-strand

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

Similar variants

TTN p.Val45fs Likely pathogenic ★ same residue
TTN p.Val45Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
TTN c.107377+1G>C Pathogenic/Likely pathogenic ★★ same condition
TTN c.54190+1G>A Pathogenic/Likely pathogenic ★★ same condition
TTN c.54811+1G>A Likely pathogenic ★★ same condition
TTN c.57112-1G>A Likely pathogenic ★★ same condition
TTN c.58732+2T>C Likely pathogenic ★★ same condition
TTN c.95723-2A>C 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-val45 (accessed [today's date]).

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