TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8416	25471;25472;25473	chr2:178717628;178717627;178717626	chr2:179582355;179582354;179582353
N2AB	8099	24520;24521;24522	chr2:178717628;178717627;178717626	chr2:179582355;179582354;179582353
N2A	7172	21739;21740;21741	chr2:178717628;178717627;178717626	chr2:179582355;179582354;179582353
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-69
• Domain position: 57
• Structural Position: 137
• Q(SASA): 0.2318
• 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	rs794729631	0.258	0.225	D	0.366	0.393	0.464270400615	gnomAD-2.1.1	1.08E-05	None	None	None	None	N	None	8.29E-05	0	None	0	0	None	3.28E-05	None	0	0	0
T/I	rs794729631	0.258	0.225	D	0.366	0.393	0.464270400615	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
T/I	rs794729631	0.258	0.225	D	0.366	0.393	0.464270400615	gnomAD-4.0.0	5.12746E-06	None	None	None	None	N	None	5.0758E-05	0	None	0	0	None	0	0	0	1.34174E-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	0.0928	likely_benign	0.1077	benign	-1.052	Destabilizing	0.426	N	0.449	neutral	N	0.488889696	None	None	N
T/C	0.4694	ambiguous	0.5131	ambiguous	-0.799	Destabilizing	1.0	D	0.614	neutral	None	None	None	None	N
T/D	0.5951	likely_pathogenic	0.704	pathogenic	-1.653	Destabilizing	0.936	D	0.582	neutral	None	None	None	None	N
T/E	0.4227	ambiguous	0.5336	ambiguous	-1.48	Destabilizing	0.98	D	0.578	neutral	None	None	None	None	N
T/F	0.208	likely_benign	0.2815	benign	-0.771	Destabilizing	0.999	D	0.632	neutral	None	None	None	None	N
T/G	0.3455	ambiguous	0.4247	ambiguous	-1.448	Destabilizing	0.992	D	0.589	neutral	None	None	None	None	N
T/H	0.2263	likely_benign	0.2848	benign	-1.685	Destabilizing	1.0	D	0.65	neutral	None	None	None	None	N
T/I	0.1418	likely_benign	0.1741	benign	-0.026	Destabilizing	0.225	N	0.366	neutral	D	0.531678251	None	None	N
T/K	0.2101	likely_benign	0.2714	benign	-0.618	Destabilizing	0.986	D	0.576	neutral	None	None	None	None	N
T/L	0.103	likely_benign	0.1252	benign	-0.026	Destabilizing	0.934	D	0.506	neutral	None	None	None	None	N
T/M	0.0908	likely_benign	0.1032	benign	0.009	Stabilizing	0.998	D	0.621	neutral	None	None	None	None	N
T/N	0.1677	likely_benign	0.2146	benign	-1.257	Destabilizing	0.975	D	0.571	neutral	N	0.489650165	None	None	N
T/P	0.7553	likely_pathogenic	0.8301	pathogenic	-0.336	Destabilizing	0.987	D	0.615	neutral	D	0.540608795	None	None	N
T/Q	0.2342	likely_benign	0.2936	benign	-1.086	Destabilizing	0.996	D	0.613	neutral	None	None	None	None	N
T/R	0.1552	likely_benign	0.21	benign	-0.786	Destabilizing	0.999	D	0.618	neutral	None	None	None	None	N
T/S	0.1134	likely_benign	0.1395	benign	-1.401	Destabilizing	0.123	N	0.345	neutral	N	0.484286949	None	None	N
T/V	0.1196	likely_benign	0.1346	benign	-0.336	Destabilizing	0.396	N	0.294	neutral	None	None	None	None	N
T/W	0.5847	likely_pathogenic	0.6978	pathogenic	-0.966	Destabilizing	1.0	D	0.673	neutral	None	None	None	None	N
T/Y	0.2542	likely_benign	0.3295	benign	-0.574	Destabilizing	1.0	D	0.629	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.