TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14890	44893;44894;44895	chr2:178624612;178624611;178624610	chr2:179489339;179489338;179489337
N2AB	13249	39970;39971;39972	chr2:178624612;178624611;178624610	chr2:179489339;179489338;179489337
N2A	12322	37189;37190;37191	chr2:178624612;178624611;178624610	chr2:179489339;179489338;179489337
N2B	5825	17698;17699;17700	chr2:178624612;178624611;178624610	chr2:179489339;179489338;179489337
Novex-1	5950	18073;18074;18075	chr2:178624612;178624611;178624610	chr2:179489339;179489338;179489337
Novex-2	6017	18274;18275;18276	chr2:178624612;178624611;178624610	chr2:179489339;179489338;179489337
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-100
• Domain position: 38
• Structural Position: 55
• Q(SASA): 0.2884
• 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/A	rs2058757156	None	0.244	N	0.233	0.138	0.158396225186	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	1.94401E-04	None	0	0	0	0	0
T/A	rs2058757156	None	0.244	N	0.233	0.138	0.158396225186	gnomAD-4.0.0	6.58068E-06	None	None	None	None	N	None	0	0	None	0	1.94401E-04	None	0	0	0	0	0
T/I	rs2154215014	None	0.784	N	0.513	0.258	0.452737964553	gnomAD-3.1.2	6.59E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.07383E-04	0
T/I	rs2154215014	None	0.784	N	0.513	0.258	0.452737964553	gnomAD-4.0.0	6.5799E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.07555E-04	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	0.1008	likely_benign	0.0827	benign	-0.416	Destabilizing	0.244	N	0.233	neutral	N	0.406170775	None	None	N
T/C	0.5358	ambiguous	0.4249	ambiguous	-0.36	Destabilizing	0.995	D	0.399	neutral	None	None	None	None	N
T/D	0.3476	ambiguous	0.2762	benign	0.429	Stabilizing	0.329	N	0.43	neutral	None	None	None	None	N
T/E	0.2351	likely_benign	0.1751	benign	0.38	Stabilizing	0.003	N	0.169	neutral	None	None	None	None	N
T/F	0.2974	likely_benign	0.2252	benign	-0.853	Destabilizing	0.981	D	0.475	neutral	None	None	None	None	N
T/G	0.3156	likely_benign	0.2676	benign	-0.569	Destabilizing	0.495	N	0.431	neutral	None	None	None	None	N
T/H	0.2338	likely_benign	0.1768	benign	-0.763	Destabilizing	0.944	D	0.467	neutral	None	None	None	None	N
T/I	0.1569	likely_benign	0.1244	benign	-0.128	Destabilizing	0.784	D	0.513	neutral	N	0.480442911	None	None	N
T/K	0.1426	likely_benign	0.1121	benign	-0.302	Destabilizing	0.01	N	0.179	neutral	N	0.415299	None	None	N
T/L	0.1315	likely_benign	0.1082	benign	-0.128	Destabilizing	0.495	N	0.445	neutral	None	None	None	None	N
T/M	0.1139	likely_benign	0.0857	benign	-0.141	Destabilizing	0.944	D	0.414	neutral	None	None	None	None	N
T/N	0.1088	likely_benign	0.092	benign	-0.194	Destabilizing	0.704	D	0.317	neutral	None	None	None	None	N
T/P	0.421	ambiguous	0.3785	ambiguous	-0.194	Destabilizing	0.784	D	0.44	neutral	N	0.51318875	None	None	N
T/Q	0.1647	likely_benign	0.1283	benign	-0.33	Destabilizing	0.004	N	0.164	neutral	None	None	None	None	N
T/R	0.1328	likely_benign	0.099	benign	-0.073	Destabilizing	0.27	N	0.45	neutral	N	0.455167949	None	None	N
T/S	0.1377	likely_benign	0.1146	benign	-0.441	Destabilizing	0.425	N	0.297	neutral	N	0.443200879	None	None	N
T/V	0.1475	likely_benign	0.1183	benign	-0.194	Destabilizing	0.665	D	0.335	neutral	None	None	None	None	N
T/W	0.5914	likely_pathogenic	0.4703	ambiguous	-0.876	Destabilizing	0.995	D	0.441	neutral	None	None	None	None	N
T/Y	0.2838	likely_benign	0.2221	benign	-0.579	Destabilizing	0.981	D	0.502	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.