TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28244	84955;84956;84957	chr2:178561402;178561401;178561400	chr2:179426129;179426128;179426127
N2AB	26603	80032;80033;80034	chr2:178561402;178561401;178561400	chr2:179426129;179426128;179426127
N2A	25676	77251;77252;77253	chr2:178561402;178561401;178561400	chr2:179426129;179426128;179426127
N2B	19179	57760;57761;57762	chr2:178561402;178561401;178561400	chr2:179426129;179426128;179426127
Novex-1	19304	58135;58136;58137	chr2:178561402;178561401;178561400	chr2:179426129;179426128;179426127
Novex-2	19371	58336;58337;58338	chr2:178561402;178561401;178561400	chr2:179426129;179426128;179426127
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGT
• RefSeq wild type template codon: ACA
• Domain: Fn3-93
• Domain position: 91
• Structural Position: 124
• Q(SASA): 0.2291
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
C/R	rs1249814057	-0.882	0.779	N	0.695	0.252	0.479056812784	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
C/R	rs1249814057	-0.882	0.779	N	0.695	0.252	0.479056812784	gnomAD-4.0.0	1.59125E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85817E-06	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
C/A	0.4643	ambiguous	0.3838	ambiguous	-1.648	Destabilizing	0.107	N	0.373	neutral	None	None	None	None	N
C/D	0.9453	likely_pathogenic	0.9156	pathogenic	-0.792	Destabilizing	0.571	D	0.652	prob.neutral	None	None	None	None	N
C/E	0.9866	likely_pathogenic	0.9776	pathogenic	-0.682	Destabilizing	0.571	D	0.645	neutral	None	None	None	None	N
C/F	0.7847	likely_pathogenic	0.7362	pathogenic	-0.977	Destabilizing	0.877	D	0.631	neutral	N	0.492732208	None	None	N
C/G	0.2281	likely_benign	0.1813	benign	-1.96	Destabilizing	0.172	N	0.585	neutral	N	0.455811403	None	None	N
C/H	0.9332	likely_pathogenic	0.9047	pathogenic	-2.08	Highly Destabilizing	0.991	D	0.737	deleterious	None	None	None	None	N
C/I	0.8836	likely_pathogenic	0.8456	pathogenic	-0.843	Destabilizing	0.73	D	0.571	neutral	None	None	None	None	N
C/K	0.9933	likely_pathogenic	0.9881	pathogenic	-1.22	Destabilizing	0.571	D	0.653	prob.neutral	None	None	None	None	N
C/L	0.8152	likely_pathogenic	0.7688	pathogenic	-0.843	Destabilizing	0.355	N	0.578	neutral	None	None	None	None	N
C/M	0.8658	likely_pathogenic	0.8411	pathogenic	0.066	Stabilizing	0.966	D	0.581	neutral	None	None	None	None	N
C/N	0.8141	likely_pathogenic	0.767	pathogenic	-1.198	Destabilizing	0.571	D	0.651	prob.neutral	None	None	None	None	N
C/P	0.9835	likely_pathogenic	0.9722	pathogenic	-1.086	Destabilizing	0.905	D	0.7	prob.delet.	None	None	None	None	N
C/Q	0.9632	likely_pathogenic	0.9395	pathogenic	-1.105	Destabilizing	0.824	D	0.713	prob.delet.	None	None	None	None	N
C/R	0.9609	likely_pathogenic	0.9321	pathogenic	-1.112	Destabilizing	0.779	D	0.695	prob.delet.	N	0.47370373	None	None	N
C/S	0.1569	likely_benign	0.1385	benign	-1.684	Destabilizing	0.002	N	0.359	neutral	N	0.284112384	None	None	N
C/T	0.3744	ambiguous	0.3208	benign	-1.404	Destabilizing	0.216	N	0.539	neutral	None	None	None	None	N
C/V	0.7179	likely_pathogenic	0.6559	pathogenic	-1.086	Destabilizing	0.571	D	0.612	neutral	None	None	None	None	N
C/W	0.9519	likely_pathogenic	0.9322	pathogenic	-1.056	Destabilizing	0.988	D	0.723	deleterious	N	0.493599	None	None	N
C/Y	0.9191	likely_pathogenic	0.8823	pathogenic	-1.012	Destabilizing	0.956	D	0.636	neutral	N	0.492905567	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.