TTN p.Ser4536Phe
c.13607C>T · rs72648905 · VCV3895250
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Absent
absent from gnomAD v4.1
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.116 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 6.7 | GERP 1.7, phastCons 1 |
| Regional constraint | o/e 0.99 | unconstrained · MANE · 141 kb · p 0.23 · regional, not allelic |
| Overall | ||
| CADD | 16.3 | PHRED · no single calibrated threshold — expert panels disagree |
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.Ser4536Phe
- Coding
- c.13607C>T
- MANE Select
- NM_001267550 · reported on NM_133379
- dbSNP
- rs72648905
- Type
- single nucleotide variant
- Location
- chr2:178748793 (GRCh38)
- Gene constraint
- LOEUF 0.479 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
- Residue 4536
- the ig-like 25 domain
Similar variants
- TTN p.Ser4536= Likely benign ★ same residue
- TTN c.100171+1G>A Likely pathogenic ★★ same type
- TTN c.100766-1G>T Likely pathogenic ★★ same type
- TTN c.100766-2A>T Likely pathogenic ★★ same type
- TTN c.106375-2A>G Pathogenic/Likely pathogenic ★★ same type
- TTN c.106531+1G>A Pathogenic/Likely pathogenic ★★ same type
- TTN c.107224-1G>C Pathogenic/Likely pathogenic ★★ same type
- TTN c.107377+1G>A Pathogenic/Likely pathogenic ★★ same type
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-ser4536phe (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown