Is TRIM63 p.Lys146fs (c.437_442delinsCC) pathogenic?

TRIM63 p.Lys146fs (c.437442delinsCC) is classified Uncertain significance in TRIM63 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-04-04). No gnomAD frequency available for this variant; Associated with cardiomyopathy, familial hypertrophic, 31.

What condition is associated with TRIM63 p.Lys146fs (c.437_442delinsCC)?

TRIM63 p.Lys146fs (c.437_442delinsCC) is associated with cardiomyopathy, familial hypertrophic, 31 (ClinVar).

How common is TRIM63 p.Lys146fs (c.437_442delinsCC) in the general population?

TRIM63 p.Lys146fs (c.437_442delinsCC) is no gnomAD frequency available for this variant (gnomAD).

TRIM63 p.Lys146fs

c.437_442delinsCC · rs2522760535 · VCV3237389

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

cardiomyopathy, familial hypertrophic, 31

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 9
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 2.3, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: TRIM63
Protein: p.Lys146fs
Coding: c.437_442delinsCC
MANE Select: NM_032588
dbSNP: rs2522760535
Type: Indel
Location: chr1:26061225 (GRCh38)
Gene constraint: LOEUF 1.329 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.88 · 3 PDB
Residue 146: the 'interaction with ttn' region; an α-helix

Full TRIM63 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

cardiomyopathy, familial hypertrophic, 31 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TRIM63 p.Ser161fs Pathogenic ★★ same condition
TRIM63 p.Cys145Tyr Conflicting classifications of pathogenicity ★ ⚠ same condition
TRIM63 p.Cys23Tyr Uncertain significance ★ ⚠ same condition
TRIM63 p.Cys75Tyr Conflicting classifications of pathogenicity ★ ⚠ same condition
TRIM63 p.Gln247Ter Conflicting classifications of pathogenicity ★ same condition
TRIM63 p.Leu319Pro 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/trim63-p-lys146fs (accessed [today's date]).

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