TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23924	71995;71996;71997	chr2:178574362;178574361;178574360	chr2:179439089;179439088;179439087
N2AB	22283	67072;67073;67074	chr2:178574362;178574361;178574360	chr2:179439089;179439088;179439087
N2A	21356	64291;64292;64293	chr2:178574362;178574361;178574360	chr2:179439089;179439088;179439087
N2B	14859	44800;44801;44802	chr2:178574362;178574361;178574360	chr2:179439089;179439088;179439087
Novex-1	14984	45175;45176;45177	chr2:178574362;178574361;178574360	chr2:179439089;179439088;179439087
Novex-2	15051	45376;45377;45378	chr2:178574362;178574361;178574360	chr2:179439089;179439088;179439087
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Fn3-62
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.5148
• 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
P/L	rs1283056884	None	1.0	N	0.736	0.513	0.468336420597	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
P/L	rs1283056884	None	1.0	N	0.736	0.513	0.468336420597	gnomAD-4.0.0	1.85937E-06	None	None	None	None	I	None	1.33543E-05	0	None	0	0	None	0	0	1.6954E-06	0	0
P/S	None	None	1.0	N	0.797	0.457	0.152612264143	gnomAD-4.0.0	1.36855E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79907E-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
P/A	0.1334	likely_benign	0.1316	benign	-0.452	Destabilizing	0.999	D	0.747	deleterious	N	0.494517063	None	None	I
P/C	0.6627	likely_pathogenic	0.6445	pathogenic	-0.672	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	I
P/D	0.7294	likely_pathogenic	0.6948	pathogenic	-0.152	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	I
P/E	0.512	ambiguous	0.4748	ambiguous	-0.237	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	I
P/F	0.7292	likely_pathogenic	0.7051	pathogenic	-0.552	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	I
P/G	0.5941	likely_pathogenic	0.5783	pathogenic	-0.593	Destabilizing	1.0	D	0.73	deleterious	None	None	None	None	I
P/H	0.3778	ambiguous	0.3579	ambiguous	0.027	Stabilizing	1.0	D	0.757	deleterious	N	0.514902723	None	None	I
P/I	0.4888	ambiguous	0.4752	ambiguous	-0.218	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	I
P/K	0.4829	ambiguous	0.4501	ambiguous	-0.373	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	I
P/L	0.225	likely_benign	0.2255	benign	-0.218	Destabilizing	1.0	D	0.736	deleterious	N	0.482235704	None	None	I
P/M	0.4922	ambiguous	0.4687	ambiguous	-0.469	Destabilizing	1.0	D	0.752	deleterious	None	None	None	None	I
P/N	0.5805	likely_pathogenic	0.5566	ambiguous	-0.2	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	I
P/Q	0.2914	likely_benign	0.2837	benign	-0.387	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	I
P/R	0.2993	likely_benign	0.2838	benign	0.119	Stabilizing	1.0	D	0.747	deleterious	N	0.496291489	None	None	I
P/S	0.2535	likely_benign	0.2501	benign	-0.594	Destabilizing	1.0	D	0.797	deleterious	N	0.473160805	None	None	I
P/T	0.2071	likely_benign	0.2047	benign	-0.573	Destabilizing	1.0	D	0.787	deleterious	N	0.514142255	None	None	I
P/V	0.334	likely_benign	0.3209	benign	-0.263	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	I
P/W	0.8928	likely_pathogenic	0.8676	pathogenic	-0.625	Destabilizing	1.0	D	0.733	deleterious	None	None	None	None	I
P/Y	0.7145	likely_pathogenic	0.6771	pathogenic	-0.338	Destabilizing	1.0	D	0.747	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.