TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23441	70546;70547;70548	chr2:178575811;178575810;178575809	chr2:179440538;179440537;179440536
N2AB	21800	65623;65624;65625	chr2:178575811;178575810;178575809	chr2:179440538;179440537;179440536
N2A	20873	62842;62843;62844	chr2:178575811;178575810;178575809	chr2:179440538;179440537;179440536
N2B	14376	43351;43352;43353	chr2:178575811;178575810;178575809	chr2:179440538;179440537;179440536
Novex-1	14501	43726;43727;43728	chr2:178575811;178575810;178575809	chr2:179440538;179440537;179440536
Novex-2	14568	43927;43928;43929	chr2:178575811;178575810;178575809	chr2:179440538;179440537;179440536
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Fn3-58
• Domain position: 7
• Structural Position: 7
• Q(SASA): 0.5199
• 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
N/K	rs751179969	0.266	0.117	N	0.287	0.12	0.126345400529	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
N/K	rs751179969	0.266	0.117	N	0.287	0.12	0.126345400529	gnomAD-4.0.0	6.84472E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99824E-07	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
N/A	0.3028	likely_benign	0.3673	ambiguous	-0.371	Destabilizing	0.966	D	0.583	neutral	None	None	None	None	I
N/C	0.3177	likely_benign	0.3915	ambiguous	0.268	Stabilizing	1.0	D	0.765	deleterious	None	None	None	None	I
N/D	0.2044	likely_benign	0.2398	benign	0.119	Stabilizing	0.977	D	0.484	neutral	N	0.515425428	None	None	I
N/E	0.5174	ambiguous	0.6121	pathogenic	0.122	Stabilizing	0.966	D	0.505	neutral	None	None	None	None	I
N/F	0.6236	likely_pathogenic	0.7026	pathogenic	-0.524	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	I
N/G	0.275	likely_benign	0.308	benign	-0.602	Destabilizing	0.983	D	0.431	neutral	None	None	None	None	I
N/H	0.1086	likely_benign	0.1273	benign	-0.52	Destabilizing	0.997	D	0.618	neutral	N	0.487215904	None	None	I
N/I	0.5426	ambiguous	0.6461	pathogenic	0.162	Stabilizing	0.997	D	0.767	deleterious	N	0.511067377	None	None	I
N/K	0.3763	ambiguous	0.4809	ambiguous	0.001	Stabilizing	0.117	N	0.287	neutral	N	0.481099837	None	None	I
N/L	0.4105	ambiguous	0.4858	ambiguous	0.162	Stabilizing	0.995	D	0.679	prob.neutral	None	None	None	None	I
N/M	0.5151	ambiguous	0.5975	pathogenic	0.405	Stabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	I
N/P	0.8574	likely_pathogenic	0.9033	pathogenic	0.013	Stabilizing	0.998	D	0.733	prob.delet.	None	None	None	None	I
N/Q	0.3507	ambiguous	0.4187	ambiguous	-0.451	Destabilizing	0.995	D	0.641	neutral	None	None	None	None	I
N/R	0.3834	ambiguous	0.4781	ambiguous	0.026	Stabilizing	0.99	D	0.588	neutral	None	None	None	None	I
N/S	0.1119	likely_benign	0.1238	benign	-0.318	Destabilizing	0.977	D	0.409	neutral	N	0.508366169	None	None	I
N/T	0.2671	likely_benign	0.3276	benign	-0.154	Destabilizing	0.977	D	0.535	neutral	N	0.492963122	None	None	I
N/V	0.5011	ambiguous	0.5997	pathogenic	0.013	Stabilizing	0.995	D	0.752	deleterious	None	None	None	None	I
N/W	0.8557	likely_pathogenic	0.9057	pathogenic	-0.451	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	I
N/Y	0.2481	likely_benign	0.3108	benign	-0.207	Destabilizing	0.999	D	0.74	deleterious	D	0.538325891	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.