TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16328	49207;49208;49209	chr2:178614532;178614531;178614530	chr2:179479259;179479258;179479257
N2AB	14687	44284;44285;44286	chr2:178614532;178614531;178614530	chr2:179479259;179479258;179479257
N2A	13760	41503;41504;41505	chr2:178614532;178614531;178614530	chr2:179479259;179479258;179479257
N2B	7263	22012;22013;22014	chr2:178614532;178614531;178614530	chr2:179479259;179479258;179479257
Novex-1	7388	22387;22388;22389	chr2:178614532;178614531;178614530	chr2:179479259;179479258;179479257
Novex-2	7455	22588;22589;22590	chr2:178614532;178614531;178614530	chr2:179479259;179479258;179479257
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: Ig-110
• Domain position: 67
• Structural Position: 153
• Q(SASA): 0.3186
• 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	rs770839243	-0.139	0.908	N	0.781	0.323	0.362361684037	gnomAD-2.1.1	1.61E-05	None	None	None	None	N	None	0	0	None	0	0	None	9.82E-05	None	0	0	1.66611E-04
T/I	rs770839243	-0.139	0.908	N	0.781	0.323	0.362361684037	gnomAD-4.0.0	6.16275E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	8.12423E-05	3.31675E-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	0.1682	likely_benign	0.2517	benign	-0.946	Destabilizing	0.581	D	0.532	neutral	D	0.531661587	None	None	N
T/C	0.5792	likely_pathogenic	0.6975	pathogenic	-0.575	Destabilizing	0.993	D	0.759	deleterious	None	None	None	None	N
T/D	0.7245	likely_pathogenic	0.8228	pathogenic	-0.067	Destabilizing	0.866	D	0.759	deleterious	None	None	None	None	N
T/E	0.6352	likely_pathogenic	0.7731	pathogenic	-0.01	Destabilizing	0.764	D	0.704	prob.neutral	None	None	None	None	N
T/F	0.5658	likely_pathogenic	0.7323	pathogenic	-0.839	Destabilizing	0.929	D	0.806	deleterious	None	None	None	None	N
T/G	0.5567	ambiguous	0.6584	pathogenic	-1.259	Destabilizing	0.866	D	0.705	prob.neutral	None	None	None	None	N
T/H	0.4712	ambiguous	0.6542	pathogenic	-1.393	Destabilizing	0.98	D	0.803	deleterious	None	None	None	None	N
T/I	0.287	likely_benign	0.4465	ambiguous	-0.186	Destabilizing	0.908	D	0.781	deleterious	N	0.510483256	None	None	N
T/K	0.3692	ambiguous	0.5919	pathogenic	-0.642	Destabilizing	0.41	N	0.635	neutral	N	0.4930014	None	None	N
T/L	0.1893	likely_benign	0.2988	benign	-0.186	Destabilizing	0.648	D	0.625	neutral	None	None	None	None	N
T/M	0.1385	likely_benign	0.222	benign	-0.058	Destabilizing	0.993	D	0.775	deleterious	None	None	None	None	N
T/N	0.2151	likely_benign	0.3019	benign	-0.728	Destabilizing	0.866	D	0.67	neutral	None	None	None	None	N
T/P	0.3607	ambiguous	0.4996	ambiguous	-0.406	Destabilizing	0.908	D	0.778	deleterious	D	0.577557694	None	None	N
T/Q	0.3699	ambiguous	0.5443	ambiguous	-0.758	Destabilizing	0.866	D	0.782	deleterious	None	None	None	None	N
T/R	0.3421	ambiguous	0.5627	ambiguous	-0.531	Destabilizing	0.01	N	0.321	neutral	N	0.511225391	None	None	N
T/S	0.2365	likely_benign	0.3207	benign	-1.08	Destabilizing	0.581	D	0.528	neutral	N	0.506845012	None	None	N
T/V	0.2204	likely_benign	0.3287	benign	-0.406	Destabilizing	0.648	D	0.584	neutral	None	None	None	None	N
T/W	0.8116	likely_pathogenic	0.9077	pathogenic	-0.783	Destabilizing	0.993	D	0.779	deleterious	None	None	None	None	N
T/Y	0.5079	ambiguous	0.6727	pathogenic	-0.535	Destabilizing	0.929	D	0.805	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.