TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27363	82312;82313;82314	chr2:178564045;178564044;178564043	chr2:179428772;179428771;179428770
N2AB	25722	77389;77390;77391	chr2:178564045;178564044;178564043	chr2:179428772;179428771;179428770
N2A	24795	74608;74609;74610	chr2:178564045;178564044;178564043	chr2:179428772;179428771;179428770
N2B	18298	55117;55118;55119	chr2:178564045;178564044;178564043	chr2:179428772;179428771;179428770
Novex-1	18423	55492;55493;55494	chr2:178564045;178564044;178564043	chr2:179428772;179428771;179428770
Novex-2	18490	55693;55694;55695	chr2:178564045;178564044;178564043	chr2:179428772;179428771;179428770
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-140
• Domain position: 86
• Structural Position: 173
• Q(SASA): 0.4773
• Predicted PPI site: I

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	None	None	0.007	N	0.3	0.222	0.272639205421	gnomAD-4.0.0	1.59134E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43275E-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	0.0735	likely_benign	0.0779	benign	-0.959	Destabilizing	0.472	N	0.506	neutral	N	0.490962205	None	None	I
T/C	0.324	likely_benign	0.3474	ambiguous	-0.641	Destabilizing	0.996	D	0.571	neutral	None	None	None	None	I
T/D	0.3228	likely_benign	0.3553	ambiguous	0.063	Stabilizing	0.59	D	0.516	neutral	None	None	None	None	I
T/E	0.2809	likely_benign	0.3049	benign	0.109	Stabilizing	0.742	D	0.553	neutral	None	None	None	None	I
T/F	0.1691	likely_benign	0.1908	benign	-0.895	Destabilizing	0.91	D	0.617	neutral	None	None	None	None	I
T/G	0.2545	likely_benign	0.2706	benign	-1.254	Destabilizing	0.742	D	0.563	neutral	None	None	None	None	I
T/H	0.1727	likely_benign	0.1924	benign	-1.424	Destabilizing	0.953	D	0.599	neutral	None	None	None	None	I
T/I	0.1012	likely_benign	0.1134	benign	-0.25	Destabilizing	0.007	N	0.3	neutral	N	0.51724473	None	None	I
T/K	0.1684	likely_benign	0.1929	benign	-0.574	Destabilizing	0.742	D	0.559	neutral	None	None	None	None	I
T/L	0.0774	likely_benign	0.0828	benign	-0.25	Destabilizing	0.17	N	0.492	neutral	None	None	None	None	I
T/M	0.074	likely_benign	0.0793	benign	-0.12	Destabilizing	0.91	D	0.592	neutral	None	None	None	None	I
T/N	0.0867	likely_benign	0.0914	benign	-0.622	Destabilizing	0.012	N	0.166	neutral	N	0.408999757	None	None	I
T/P	0.1851	likely_benign	0.2037	benign	-0.454	Destabilizing	0.979	D	0.619	neutral	D	0.531424748	None	None	I
T/Q	0.1959	likely_benign	0.2101	benign	-0.698	Destabilizing	0.953	D	0.617	neutral	None	None	None	None	I
T/R	0.1358	likely_benign	0.1584	benign	-0.472	Destabilizing	0.953	D	0.604	neutral	None	None	None	None	I
T/S	0.0981	likely_benign	0.1047	benign	-1.009	Destabilizing	0.472	N	0.5	neutral	N	0.467775915	None	None	I
T/V	0.0932	likely_benign	0.1012	benign	-0.454	Destabilizing	0.17	N	0.501	neutral	None	None	None	None	I
T/W	0.4684	ambiguous	0.5076	ambiguous	-0.794	Destabilizing	0.996	D	0.604	neutral	None	None	None	None	I
T/Y	0.1937	likely_benign	0.2071	benign	-0.55	Destabilizing	0.953	D	0.623	neutral	None	None	None	None	I

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.