TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20656	62191;62192;62193	chr2:178589759;178589758;178589757	chr2:179454486;179454485;179454484
N2AB	19015	57268;57269;57270	chr2:178589759;178589758;178589757	chr2:179454486;179454485;179454484
N2A	18088	54487;54488;54489	chr2:178589759;178589758;178589757	chr2:179454486;179454485;179454484
N2B	11591	34996;34997;34998	chr2:178589759;178589758;178589757	chr2:179454486;179454485;179454484
Novex-1	11716	35371;35372;35373	chr2:178589759;178589758;178589757	chr2:179454486;179454485;179454484
Novex-2	11783	35572;35573;35574	chr2:178589759;178589758;178589757	chr2:179454486;179454485;179454484
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-37
• Domain position: 88
• Structural Position: 123
• Q(SASA): 0.2365
• 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
T/I	rs1363633199	None	0.999	N	0.898	0.363	0.314716216878	gnomAD-4.0.0	2.73722E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.59833E-06	0	0
T/K	rs1363633199	None	0.999	N	0.883	0.361	0.382087116544	gnomAD-4.0.0	6.84305E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.65684E-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
T/A	0.5332	ambiguous	0.4745	ambiguous	-0.73	Destabilizing	0.997	D	0.663	prob.neutral	N	0.511454042	None	None	N
T/C	0.8789	likely_pathogenic	0.8506	pathogenic	-0.323	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
T/D	0.949	likely_pathogenic	0.9347	pathogenic	-0.391	Destabilizing	0.999	D	0.884	deleterious	None	None	None	None	N
T/E	0.9461	likely_pathogenic	0.9281	pathogenic	-0.238	Destabilizing	0.999	D	0.884	deleterious	None	None	None	None	N
T/F	0.9347	likely_pathogenic	0.9189	pathogenic	-0.431	Destabilizing	0.999	D	0.899	deleterious	None	None	None	None	N
T/G	0.7692	likely_pathogenic	0.7342	pathogenic	-1.112	Destabilizing	0.999	D	0.847	deleterious	None	None	None	None	N
T/H	0.9482	likely_pathogenic	0.9351	pathogenic	-1.22	Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	N
T/I	0.8066	likely_pathogenic	0.7885	pathogenic	0.247	Stabilizing	0.999	D	0.898	deleterious	N	0.505277431	None	None	N
T/K	0.9562	likely_pathogenic	0.9402	pathogenic	-0.187	Destabilizing	0.999	D	0.883	deleterious	N	0.498179091	None	None	N
T/L	0.4019	ambiguous	0.4229	ambiguous	0.247	Stabilizing	0.998	D	0.801	deleterious	None	None	None	None	N
T/M	0.3619	ambiguous	0.362	ambiguous	0.102	Stabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
T/N	0.638	likely_pathogenic	0.5935	pathogenic	-0.603	Destabilizing	0.999	D	0.804	deleterious	None	None	None	None	N
T/P	0.909	likely_pathogenic	0.8997	pathogenic	-0.046	Destabilizing	0.999	D	0.877	deleterious	N	0.487363674	None	None	N
T/Q	0.9211	likely_pathogenic	0.902	pathogenic	-0.443	Destabilizing	0.999	D	0.872	deleterious	None	None	None	None	N
T/R	0.9578	likely_pathogenic	0.9357	pathogenic	-0.36	Destabilizing	0.999	D	0.883	deleterious	N	0.486404712	None	None	N
T/S	0.4182	ambiguous	0.3701	ambiguous	-0.892	Destabilizing	0.997	D	0.663	prob.neutral	N	0.466836473	None	None	N
T/V	0.6536	likely_pathogenic	0.6291	pathogenic	-0.046	Destabilizing	0.998	D	0.729	deleterious	None	None	None	None	N
T/W	0.9868	likely_pathogenic	0.9832	pathogenic	-0.545	Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
T/Y	0.9539	likely_pathogenic	0.9356	pathogenic	-0.162	Destabilizing	1.0	D	0.907	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.