TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30576	91951;91952;91953	chr2:178550112;178550111;178550110	chr2:179414839;179414838;179414837
N2AB	28935	87028;87029;87030	chr2:178550112;178550111;178550110	chr2:179414839;179414838;179414837
N2A	28008	84247;84248;84249	chr2:178550112;178550111;178550110	chr2:179414839;179414838;179414837
N2B	21511	64756;64757;64758	chr2:178550112;178550111;178550110	chr2:179414839;179414838;179414837
Novex-1	21636	65131;65132;65133	chr2:178550112;178550111;178550110	chr2:179414839;179414838;179414837
Novex-2	21703	65332;65333;65334	chr2:178550112;178550111;178550110	chr2:179414839;179414838;179414837
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-149
• Domain position: 45
• Structural Position: 125
• Q(SASA): 0.4802
• 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/A	None	None	0.76	N	0.443	0.187	0.344251166708	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	1.01626E-03	None	0	0	None	0	0	0	0	0
T/N	rs1170381961	None	0.982	N	0.541	0.265	0.578910049572	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
T/N	rs1170381961	None	0.982	N	0.541	0.265	0.578910049572	gnomAD-4.0.0	6.57471E-06	None	None	None	None	I	None	2.41488E-05	0	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
T/A	0.1034	likely_benign	0.1018	benign	-0.583	Destabilizing	0.76	D	0.443	neutral	N	0.474261957	None	None	I
T/C	0.4146	ambiguous	0.4141	ambiguous	-0.28	Destabilizing	0.999	D	0.607	neutral	None	None	None	None	I
T/D	0.5849	likely_pathogenic	0.5951	pathogenic	-0.102	Destabilizing	0.986	D	0.575	neutral	None	None	None	None	I
T/E	0.4708	ambiguous	0.4718	ambiguous	-0.169	Destabilizing	0.986	D	0.58	neutral	None	None	None	None	I
T/F	0.3292	likely_benign	0.335	benign	-1.015	Destabilizing	0.998	D	0.649	neutral	None	None	None	None	I
T/G	0.291	likely_benign	0.2866	benign	-0.74	Destabilizing	0.91	D	0.551	neutral	None	None	None	None	I
T/H	0.291	likely_benign	0.298	benign	-1.099	Destabilizing	0.999	D	0.615	neutral	None	None	None	None	I
T/I	0.2157	likely_benign	0.2194	benign	-0.282	Destabilizing	0.991	D	0.633	neutral	N	0.473397952	None	None	I
T/K	0.3148	likely_benign	0.3296	benign	-0.489	Destabilizing	0.986	D	0.579	neutral	None	None	None	None	I
T/L	0.1406	likely_benign	0.1427	benign	-0.282	Destabilizing	0.953	D	0.559	neutral	None	None	None	None	I
T/M	0.1036	likely_benign	0.1073	benign	0.119	Stabilizing	0.999	D	0.607	neutral	None	None	None	None	I
T/N	0.1579	likely_benign	0.1547	benign	-0.283	Destabilizing	0.982	D	0.541	neutral	N	0.504758222	None	None	I
T/P	0.6058	likely_pathogenic	0.5941	pathogenic	-0.353	Destabilizing	0.991	D	0.632	neutral	D	0.527904441	None	None	I
T/Q	0.2919	likely_benign	0.298	benign	-0.576	Destabilizing	0.993	D	0.635	neutral	None	None	None	None	I
T/R	0.2596	likely_benign	0.2697	benign	-0.172	Destabilizing	0.986	D	0.631	neutral	None	None	None	None	I
T/S	0.1137	likely_benign	0.1139	benign	-0.509	Destabilizing	0.17	N	0.235	neutral	N	0.439802666	None	None	I
T/V	0.1657	likely_benign	0.1661	benign	-0.353	Destabilizing	0.953	D	0.515	neutral	None	None	None	None	I
T/W	0.6543	likely_pathogenic	0.6718	pathogenic	-0.956	Destabilizing	0.999	D	0.649	neutral	None	None	None	None	I
T/Y	0.3721	ambiguous	0.3677	ambiguous	-0.7	Destabilizing	0.998	D	0.641	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.