TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28160	84703;84704;84705	chr2:178561654;178561653;178561652	chr2:179426381;179426380;179426379
N2AB	26519	79780;79781;79782	chr2:178561654;178561653;178561652	chr2:179426381;179426380;179426379
N2A	25592	76999;77000;77001	chr2:178561654;178561653;178561652	chr2:179426381;179426380;179426379
N2B	19095	57508;57509;57510	chr2:178561654;178561653;178561652	chr2:179426381;179426380;179426379
Novex-1	19220	57883;57884;57885	chr2:178561654;178561653;178561652	chr2:179426381;179426380;179426379
Novex-2	19287	58084;58085;58086	chr2:178561654;178561653;178561652	chr2:179426381;179426380;179426379
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: Fn3-93
• Domain position: 7
• Structural Position: 7
• Q(SASA): 0.6393
• 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	0.873	N	0.433	0.243	0.361558571881	gnomAD-4.0.0	1.60568E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.88472E-06	0	0
T/P	rs985003893	None	0.003	N	0.197	0.161	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
T/P	rs985003893	None	0.003	N	0.197	0.161	None	gnomAD-4.0.0	1.18164E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.5299E-05	0	1.60865E-05

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	0.1476	likely_benign	0.1268	benign	-0.744	Destabilizing	0.005	N	0.082	neutral	N	0.471245002	None	None	I
T/C	0.5856	likely_pathogenic	0.5221	ambiguous	-0.463	Destabilizing	0.991	D	0.381	neutral	None	None	None	None	I
T/D	0.7364	likely_pathogenic	0.689	pathogenic	-0.421	Destabilizing	0.39	N	0.361	neutral	None	None	None	None	I
T/E	0.5454	ambiguous	0.5049	ambiguous	-0.45	Destabilizing	0.561	D	0.343	neutral	None	None	None	None	I
T/F	0.4033	ambiguous	0.334	benign	-0.906	Destabilizing	0.965	D	0.381	neutral	None	None	None	None	I
T/G	0.5786	likely_pathogenic	0.5175	ambiguous	-0.968	Destabilizing	0.345	N	0.328	neutral	None	None	None	None	I
T/H	0.4581	ambiguous	0.4002	ambiguous	-1.284	Destabilizing	0.901	D	0.359	neutral	None	None	None	None	I
T/I	0.1896	likely_benign	0.1609	benign	-0.245	Destabilizing	0.873	D	0.433	neutral	N	0.471938436	None	None	I
T/K	0.3394	likely_benign	0.296	benign	-0.771	Destabilizing	0.017	N	0.183	neutral	None	None	None	None	I
T/L	0.141	likely_benign	0.1163	benign	-0.245	Destabilizing	0.561	D	0.342	neutral	None	None	None	None	I
T/M	0.1075	likely_benign	0.0915	benign	0.135	Stabilizing	0.965	D	0.396	neutral	None	None	None	None	I
T/N	0.2176	likely_benign	0.1856	benign	-0.624	Destabilizing	0.013	N	0.256	neutral	N	0.431835678	None	None	I
T/P	0.1661	likely_benign	0.1375	benign	-0.38	Destabilizing	0.003	N	0.197	neutral	N	0.457835775	None	None	I
T/Q	0.3395	likely_benign	0.3031	benign	-0.885	Destabilizing	0.818	D	0.434	neutral	None	None	None	None	I
T/R	0.3403	ambiguous	0.2859	benign	-0.454	Destabilizing	0.39	N	0.412	neutral	None	None	None	None	I
T/S	0.2157	likely_benign	0.1844	benign	-0.862	Destabilizing	0.036	N	0.111	neutral	N	0.470957001	None	None	I
T/V	0.1705	likely_benign	0.144	benign	-0.38	Destabilizing	0.561	D	0.27	neutral	None	None	None	None	I
T/W	0.8001	likely_pathogenic	0.756	pathogenic	-0.822	Destabilizing	0.991	D	0.443	neutral	None	None	None	None	I
T/Y	0.4363	ambiguous	0.3866	ambiguous	-0.599	Destabilizing	0.965	D	0.381	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.