TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19165	57718;57719;57720	chr2:178597589;178597588;178597587	chr2:179462316;179462315;179462314
N2AB	17524	52795;52796;52797	chr2:178597589;178597588;178597587	chr2:179462316;179462315;179462314
N2A	16597	50014;50015;50016	chr2:178597589;178597588;178597587	chr2:179462316;179462315;179462314
N2B	10100	30523;30524;30525	chr2:178597589;178597588;178597587	chr2:179462316;179462315;179462314
Novex-1	10225	30898;30899;30900	chr2:178597589;178597588;178597587	chr2:179462316;179462315;179462314
Novex-2	10292	31099;31100;31101	chr2:178597589;178597588;178597587	chr2:179462316;179462315;179462314
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Ig-117
• Domain position: 71
• Structural Position: 158
• Q(SASA): 0.1864
• Predicted PPI site: I

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
A/D	None	None	1.0	D	0.807	0.78	0.773638986022	gnomAD-4.0.0	1.59354E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43575E-05	0
A/T	None	None	1.0	D	0.712	0.64	0.654251013966	gnomAD-4.0.0	6.8461E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99696E-07	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
A/C	0.6316	likely_pathogenic	0.6665	pathogenic	-1.069	Destabilizing	1.0	D	0.776	deleterious	None	None	None	None	I
A/D	0.9973	likely_pathogenic	0.9972	pathogenic	-2.001	Highly Destabilizing	1.0	D	0.807	deleterious	D	0.613694675	None	None	I
A/E	0.99	likely_pathogenic	0.9892	pathogenic	-1.972	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	I
A/F	0.9336	likely_pathogenic	0.9419	pathogenic	-0.997	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	I
A/G	0.3727	ambiguous	0.4186	ambiguous	-1.432	Destabilizing	1.0	D	0.53	neutral	D	0.597039541	None	None	I
A/H	0.9953	likely_pathogenic	0.9953	pathogenic	-1.758	Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	I
A/I	0.5526	ambiguous	0.6308	pathogenic	-0.343	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	I
A/K	0.9973	likely_pathogenic	0.9974	pathogenic	-1.518	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	I
A/L	0.4037	ambiguous	0.467	ambiguous	-0.343	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	I
A/M	0.7267	likely_pathogenic	0.7779	pathogenic	-0.282	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	I
A/N	0.9911	likely_pathogenic	0.9917	pathogenic	-1.347	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	I
A/P	0.9888	likely_pathogenic	0.9899	pathogenic	-0.557	Destabilizing	1.0	D	0.804	deleterious	D	0.61349287	None	None	I
A/Q	0.9802	likely_pathogenic	0.9794	pathogenic	-1.431	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	I
A/R	0.9908	likely_pathogenic	0.9905	pathogenic	-1.239	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	I
A/S	0.4742	ambiguous	0.502	ambiguous	-1.665	Destabilizing	1.0	D	0.543	neutral	D	0.58755115	None	None	I
A/T	0.5495	ambiguous	0.6086	pathogenic	-1.548	Destabilizing	1.0	D	0.712	prob.delet.	D	0.612887458	None	None	I
A/V	0.2652	likely_benign	0.337	benign	-0.557	Destabilizing	1.0	D	0.606	neutral	D	0.524947067	None	None	I
A/W	0.9962	likely_pathogenic	0.9966	pathogenic	-1.51	Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	I
A/Y	0.9843	likely_pathogenic	0.9861	pathogenic	-1.093	Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	I

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.