TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26783	80572;80573;80574	chr2:178565785;178565784;178565783	chr2:179430512;179430511;179430510
N2AB	25142	75649;75650;75651	chr2:178565785;178565784;178565783	chr2:179430512;179430511;179430510
N2A	24215	72868;72869;72870	chr2:178565785;178565784;178565783	chr2:179430512;179430511;179430510
N2B	17718	53377;53378;53379	chr2:178565785;178565784;178565783	chr2:179430512;179430511;179430510
Novex-1	17843	53752;53753;53754	chr2:178565785;178565784;178565783	chr2:179430512;179430511;179430510
Novex-2	17910	53953;53954;53955	chr2:178565785;178565784;178565783	chr2:179430512;179430511;179430510
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-83
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.1899
• 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
P/S	None	None	0.262	N	0.495	0.205	0.231231049324	gnomAD-4.0.0	1.59167E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43279E-05	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
P/A	0.0916	likely_benign	0.0948	benign	-1.634	Destabilizing	0.094	N	0.545	neutral	N	0.48417144	None	None	N
P/C	0.5323	ambiguous	0.5427	ambiguous	-1.539	Destabilizing	0.999	D	0.856	deleterious	None	None	None	None	N
P/D	0.9161	likely_pathogenic	0.9057	pathogenic	-2.622	Highly Destabilizing	0.897	D	0.813	deleterious	None	None	None	None	N
P/E	0.6743	likely_pathogenic	0.6643	pathogenic	-2.601	Highly Destabilizing	0.798	D	0.815	deleterious	None	None	None	None	N
P/F	0.7033	likely_pathogenic	0.6415	pathogenic	-1.302	Destabilizing	0.999	D	0.881	deleterious	None	None	None	None	N
P/G	0.6219	likely_pathogenic	0.6013	pathogenic	-1.938	Destabilizing	0.927	D	0.789	deleterious	None	None	None	None	N
P/H	0.5065	ambiguous	0.462	ambiguous	-1.395	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
P/I	0.4038	ambiguous	0.3996	ambiguous	-0.874	Destabilizing	0.999	D	0.875	deleterious	None	None	None	None	N
P/K	0.7246	likely_pathogenic	0.7087	pathogenic	-1.342	Destabilizing	0.992	D	0.815	deleterious	None	None	None	None	N
P/L	0.2571	likely_benign	0.238	benign	-0.874	Destabilizing	0.997	D	0.817	deleterious	D	0.535168658	None	None	N
P/M	0.4752	ambiguous	0.4394	ambiguous	-0.895	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
P/N	0.7703	likely_pathogenic	0.7401	pathogenic	-1.388	Destabilizing	0.982	D	0.851	deleterious	None	None	None	None	N
P/Q	0.4186	ambiguous	0.3795	ambiguous	-1.616	Destabilizing	0.992	D	0.802	deleterious	N	0.503933671	None	None	N
P/R	0.5593	ambiguous	0.5306	ambiguous	-0.831	Destabilizing	0.997	D	0.859	deleterious	N	0.49966771	None	None	N
P/S	0.2106	likely_benign	0.1982	benign	-1.779	Destabilizing	0.262	N	0.495	neutral	N	0.488538441	None	None	N
P/T	0.2611	likely_benign	0.2546	benign	-1.663	Destabilizing	0.855	D	0.803	deleterious	N	0.502567773	None	None	N
P/V	0.2596	likely_benign	0.2636	benign	-1.098	Destabilizing	0.987	D	0.821	deleterious	None	None	None	None	N
P/W	0.8924	likely_pathogenic	0.8707	pathogenic	-1.525	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
P/Y	0.7431	likely_pathogenic	0.7019	pathogenic	-1.216	Destabilizing	1.0	D	0.881	deleterious	None	None	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.