TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16315	49168;49169;49170	chr2:178614571;178614570;178614569	chr2:179479298;179479297;179479296
N2AB	14674	44245;44246;44247	chr2:178614571;178614570;178614569	chr2:179479298;179479297;179479296
N2A	13747	41464;41465;41466	chr2:178614571;178614570;178614569	chr2:179479298;179479297;179479296
N2B	7250	21973;21974;21975	chr2:178614571;178614570;178614569	chr2:179479298;179479297;179479296
Novex-1	7375	22348;22349;22350	chr2:178614571;178614570;178614569	chr2:179479298;179479297;179479296
Novex-2	7442	22549;22550;22551	chr2:178614571;178614570;178614569	chr2:179479298;179479297;179479296
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: 54
• Structural Position: 137
• Q(SASA): 0.1459
• 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/P	rs760198616	-0.532	0.997	D	0.621	0.698	0.513503867364	gnomAD-2.1.1	8.07E-06	None	None	None	None	N	None	0	0	None	0	0	None	6.54E-05	None	0	0	0
T/P	rs760198616	-0.532	0.997	D	0.621	0.698	0.513503867364	gnomAD-4.0.0	2.05414E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	3.47955E-05	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
T/A	0.1087	likely_benign	0.1108	benign	-0.917	Destabilizing	0.939	D	0.533	neutral	D	0.565945881	None	None	N
T/C	0.3282	likely_benign	0.317	benign	-0.872	Destabilizing	0.999	D	0.64	neutral	None	None	None	None	N
T/D	0.6994	likely_pathogenic	0.7239	pathogenic	-1.808	Destabilizing	0.998	D	0.625	neutral	None	None	None	None	N
T/E	0.5022	ambiguous	0.5077	ambiguous	-1.665	Destabilizing	0.998	D	0.621	neutral	None	None	None	None	N
T/F	0.2517	likely_benign	0.279	benign	-0.713	Destabilizing	0.986	D	0.643	neutral	None	None	None	None	N
T/G	0.4563	ambiguous	0.4328	ambiguous	-1.293	Destabilizing	0.998	D	0.643	neutral	None	None	None	None	N
T/H	0.3	likely_benign	0.3165	benign	-1.627	Destabilizing	0.999	D	0.672	neutral	None	None	None	None	N
T/I	0.1141	likely_benign	0.1172	benign	0.04	Stabilizing	0.046	N	0.389	neutral	N	0.513806502	None	None	N
T/K	0.2326	likely_benign	0.2325	benign	-0.827	Destabilizing	0.991	D	0.623	neutral	N	0.508132733	None	None	N
T/L	0.0958	likely_benign	0.0935	benign	0.04	Stabilizing	0.807	D	0.547	neutral	None	None	None	None	N
T/M	0.0782	likely_benign	0.0792	benign	0.17	Stabilizing	0.996	D	0.642	neutral	None	None	None	None	N
T/N	0.2225	likely_benign	0.2278	benign	-1.441	Destabilizing	0.998	D	0.633	neutral	None	None	None	None	N
T/P	0.883	likely_pathogenic	0.911	pathogenic	-0.246	Destabilizing	0.997	D	0.621	neutral	D	0.673261331	None	None	N
T/Q	0.3049	likely_benign	0.3031	benign	-1.336	Destabilizing	0.998	D	0.639	neutral	None	None	None	None	N
T/R	0.2049	likely_benign	0.2099	benign	-0.912	Destabilizing	0.997	D	0.622	neutral	N	0.510103165	None	None	N
T/S	0.1683	likely_benign	0.1699	benign	-1.516	Destabilizing	0.969	D	0.537	neutral	N	0.510764803	None	None	N
T/V	0.0883	likely_benign	0.085	benign	-0.246	Destabilizing	0.807	D	0.528	neutral	None	None	None	None	N
T/W	0.6461	likely_pathogenic	0.6608	pathogenic	-0.913	Destabilizing	0.999	D	0.665	neutral	None	None	None	None	N
T/Y	0.3334	likely_benign	0.3543	ambiguous	-0.532	Destabilizing	0.998	D	0.671	neutral	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.