TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2642	8149;8150;8151	chr2:178771403;178771402;178771401	chr2:179636130;179636129;179636128
N2AB	2642	8149;8150;8151	chr2:178771403;178771402;178771401	chr2:179636130;179636129;179636128
N2A	2642	8149;8150;8151	chr2:178771403;178771402;178771401	chr2:179636130;179636129;179636128
N2B	2596	8011;8012;8013	chr2:178771403;178771402;178771401	chr2:179636130;179636129;179636128
Novex-1	2596	8011;8012;8013	chr2:178771403;178771402;178771401	chr2:179636130;179636129;179636128
Novex-2	2596	8011;8012;8013	chr2:178771403;178771402;178771401	chr2:179636130;179636129;179636128
Novex-3	2642	8149;8150;8151	chr2:178771403;178771402;178771401	chr2:179636130;179636129;179636128

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-16
• Domain position: 22
• Structural Position: 34
• Q(SASA): 0.2414
• 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
E/G	None	None	0.999	D	0.748	0.581	0.527251791467	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-05	0
E/K	None	None	0.992	D	0.509	0.426	0.377097596864	gnomAD-4.0.0	1.59089E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85734E-06	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
E/A	0.2402	likely_benign	0.2514	benign	-0.714	Destabilizing	0.996	D	0.605	neutral	D	0.614432328	None	None	N
E/C	0.9181	likely_pathogenic	0.9164	pathogenic	-0.569	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
E/D	0.3367	likely_benign	0.361	ambiguous	-1.362	Destabilizing	0.998	D	0.453	neutral	D	0.642114925	None	None	N
E/F	0.8203	likely_pathogenic	0.8354	pathogenic	-0.73	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
E/G	0.4097	ambiguous	0.4359	ambiguous	-1.054	Destabilizing	0.999	D	0.748	deleterious	D	0.578590162	None	None	N
E/H	0.6185	likely_pathogenic	0.616	pathogenic	-1.181	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
E/I	0.365	ambiguous	0.3802	ambiguous	0.203	Stabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
E/K	0.1957	likely_benign	0.2085	benign	-1.028	Destabilizing	0.992	D	0.509	neutral	D	0.557828307	None	None	N
E/L	0.5018	ambiguous	0.5207	ambiguous	0.203	Stabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
E/M	0.5025	ambiguous	0.5115	ambiguous	0.688	Stabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
E/N	0.4908	ambiguous	0.5258	ambiguous	-1.233	Destabilizing	1.0	D	0.712	prob.delet.	None	None	None	None	N
E/P	0.9797	likely_pathogenic	0.9804	pathogenic	-0.081	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
E/Q	0.1797	likely_benign	0.1864	benign	-1.089	Destabilizing	0.957	D	0.224	neutral	N	0.502125148	None	None	N
E/R	0.351	ambiguous	0.368	ambiguous	-0.958	Destabilizing	0.999	D	0.703	prob.neutral	None	None	None	None	N
E/S	0.35	ambiguous	0.3707	ambiguous	-1.608	Destabilizing	0.997	D	0.547	neutral	None	None	None	None	N
E/T	0.2985	likely_benign	0.3201	benign	-1.331	Destabilizing	1.0	D	0.766	deleterious	None	None	None	None	N
E/V	0.2382	likely_benign	0.2451	benign	-0.081	Destabilizing	0.999	D	0.807	deleterious	D	0.588195356	None	None	N
E/W	0.9353	likely_pathogenic	0.9374	pathogenic	-0.8	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
E/Y	0.7575	likely_pathogenic	0.7682	pathogenic	-0.576	Destabilizing	1.0	D	0.821	deleterious	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.