TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16367	49324;49325;49326	chr2:178614298;178614297;178614296	chr2:179479025;179479024;179479023
N2AB	14726	44401;44402;44403	chr2:178614298;178614297;178614296	chr2:179479025;179479024;179479023
N2A	13799	41620;41621;41622	chr2:178614298;178614297;178614296	chr2:179479025;179479024;179479023
N2B	7302	22129;22130;22131	chr2:178614298;178614297;178614296	chr2:179479025;179479024;179479023
Novex-1	7427	22504;22505;22506	chr2:178614298;178614297;178614296	chr2:179479025;179479024;179479023
Novex-2	7494	22705;22706;22707	chr2:178614298;178614297;178614296	chr2:179479025;179479024;179479023
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Fn3-6
• Domain position: 17
• Structural Position: 19
• Q(SASA): 0.1064
• 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
S/L	None	None	0.989	D	0.665	0.513	0.829753570234	gnomAD-4.0.0	3.18638E-06	None	None	None	None	N	None	0	4.57875E-05	None	0	0	None	0	0	0	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
S/A	0.1489	likely_benign	0.158	benign	-0.228	Destabilizing	0.973	D	0.428	neutral	D	0.526997544	None	None	N
S/C	0.1468	likely_benign	0.1574	benign	-0.601	Destabilizing	1.0	D	0.752	deleterious	None	None	None	None	N
S/D	0.751	likely_pathogenic	0.7771	pathogenic	-1.825	Destabilizing	0.996	D	0.505	neutral	None	None	None	None	N
S/E	0.7941	likely_pathogenic	0.798	pathogenic	-1.799	Destabilizing	0.996	D	0.508	neutral	None	None	None	None	N
S/F	0.2207	likely_benign	0.2133	benign	-0.644	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
S/G	0.172	likely_benign	0.1815	benign	-0.454	Destabilizing	0.996	D	0.435	neutral	None	None	None	None	N
S/H	0.4428	ambiguous	0.4223	ambiguous	-1.084	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
S/I	0.4545	ambiguous	0.4713	ambiguous	0.265	Stabilizing	0.998	D	0.814	deleterious	None	None	None	None	N
S/K	0.92	likely_pathogenic	0.9209	pathogenic	-0.644	Destabilizing	0.996	D	0.501	neutral	None	None	None	None	N
S/L	0.233	likely_benign	0.2362	benign	0.265	Stabilizing	0.989	D	0.665	neutral	D	0.70403064	None	None	N
S/M	0.268	likely_benign	0.261	benign	0.548	Stabilizing	1.0	D	0.764	deleterious	None	None	None	None	N
S/N	0.2473	likely_benign	0.258	benign	-1.057	Destabilizing	0.996	D	0.517	neutral	None	None	None	None	N
S/P	0.9945	likely_pathogenic	0.9952	pathogenic	0.133	Stabilizing	0.999	D	0.762	deleterious	D	0.775195198	None	None	N
S/Q	0.7423	likely_pathogenic	0.7215	pathogenic	-1.276	Destabilizing	1.0	D	0.659	neutral	None	None	None	None	N
S/R	0.8865	likely_pathogenic	0.8918	pathogenic	-0.491	Destabilizing	0.999	D	0.785	deleterious	None	None	None	None	N
S/T	0.1089	likely_benign	0.1111	benign	-0.747	Destabilizing	0.543	D	0.355	neutral	N	0.492684732	None	None	N
S/V	0.4198	ambiguous	0.4261	ambiguous	0.133	Stabilizing	0.998	D	0.729	prob.delet.	None	None	None	None	N
S/W	0.4843	ambiguous	0.4724	ambiguous	-0.839	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
S/Y	0.1994	likely_benign	0.1959	benign	-0.408	Destabilizing	1.0	D	0.817	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.