TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17050	51373;51374;51375	chr2:178610378;178610377;178610376	chr2:179475105;179475104;179475103
N2AB	15409	46450;46451;46452	chr2:178610378;178610377;178610376	chr2:179475105;179475104;179475103
N2A	14482	43669;43670;43671	chr2:178610378;178610377;178610376	chr2:179475105;179475104;179475103
N2B	7985	24178;24179;24180	chr2:178610378;178610377;178610376	chr2:179475105;179475104;179475103
Novex-1	8110	24553;24554;24555	chr2:178610378;178610377;178610376	chr2:179475105;179475104;179475103
Novex-2	8177	24754;24755;24756	chr2:178610378;178610377;178610376	chr2:179475105;179475104;179475103
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: Fn3-12
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.2377
• 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/Q	None	None	0.362	N	0.346	0.144	0.279370189704	gnomAD-4.0.0	4.10941E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.50019E-06	0	1.65898E-05

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	0.0777	likely_benign	0.0838	benign	-1.24	Destabilizing	0.977	D	0.502	neutral	N	0.461236252	None	None	N
P/C	0.5543	ambiguous	0.5856	pathogenic	-0.656	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
P/D	0.6597	likely_pathogenic	0.6499	pathogenic	-1.177	Destabilizing	0.995	D	0.693	prob.neutral	None	None	None	None	N
P/E	0.3339	likely_benign	0.338	benign	-1.261	Destabilizing	0.966	D	0.541	neutral	None	None	None	None	N
P/F	0.6241	likely_pathogenic	0.648	pathogenic	-1.244	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
P/G	0.4382	ambiguous	0.4513	ambiguous	-1.464	Destabilizing	0.995	D	0.671	neutral	None	None	None	None	N
P/H	0.2771	likely_benign	0.2949	benign	-1.019	Destabilizing	0.999	D	0.803	deleterious	None	None	None	None	N
P/I	0.3188	likely_benign	0.3593	ambiguous	-0.755	Destabilizing	0.998	D	0.812	deleterious	None	None	None	None	N
P/K	0.3054	likely_benign	0.307	benign	-0.929	Destabilizing	0.966	D	0.628	neutral	None	None	None	None	N
P/L	0.1839	likely_benign	0.1977	benign	-0.755	Destabilizing	0.993	D	0.751	deleterious	D	0.612183156	None	None	N
P/M	0.3617	ambiguous	0.406	ambiguous	-0.428	Destabilizing	0.999	D	0.803	deleterious	None	None	None	None	N
P/N	0.427	ambiguous	0.4592	ambiguous	-0.535	Destabilizing	0.995	D	0.753	deleterious	None	None	None	None	N
P/Q	0.1472	likely_benign	0.165	benign	-0.847	Destabilizing	0.362	N	0.346	neutral	N	0.481110344	None	None	N
P/R	0.2267	likely_benign	0.2216	benign	-0.314	Destabilizing	0.987	D	0.748	deleterious	N	0.521460974	None	None	N
P/S	0.1669	likely_benign	0.1882	benign	-0.937	Destabilizing	0.993	D	0.665	neutral	N	0.468864522	None	None	N
P/T	0.143	likely_benign	0.1661	benign	-0.93	Destabilizing	0.993	D	0.707	prob.neutral	D	0.548816229	None	None	N
P/V	0.2282	likely_benign	0.2534	benign	-0.882	Destabilizing	0.998	D	0.733	prob.delet.	None	None	None	None	N
P/W	0.8359	likely_pathogenic	0.8365	pathogenic	-1.318	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
P/Y	0.6142	likely_pathogenic	0.6424	pathogenic	-1.064	Destabilizing	0.999	D	0.813	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.