TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23512	70759;70760;70761	chr2:178575598;178575597;178575596	chr2:179440325;179440324;179440323
N2AB	21871	65836;65837;65838	chr2:178575598;178575597;178575596	chr2:179440325;179440324;179440323
N2A	20944	63055;63056;63057	chr2:178575598;178575597;178575596	chr2:179440325;179440324;179440323
N2B	14447	43564;43565;43566	chr2:178575598;178575597;178575596	chr2:179440325;179440324;179440323
Novex-1	14572	43939;43940;43941	chr2:178575598;178575597;178575596	chr2:179440325;179440324;179440323
Novex-2	14639	44140;44141;44142	chr2:178575598;178575597;178575596	chr2:179440325;179440324;179440323
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-58
• Domain position: 78
• Structural Position: 111
• Q(SASA): 0.2266
• 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
E/D	None	None	0.974	N	0.459	0.342	0.335910606209	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	6.07533E-05	0
E/G	None	None	1.0	N	0.765	0.585	0.459906663326	gnomAD-4.0.0	1.59157E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85914E-06	0	0
E/K	rs752696466	-0.669	0.998	N	0.538	0.388	0.315609569513	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
E/K	rs752696466	-0.669	0.998	N	0.538	0.388	0.315609569513	gnomAD-4.0.0	1.59154E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43299E-05	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	0.5104	ambiguous	0.5779	pathogenic	-0.633	Destabilizing	0.997	D	0.677	prob.neutral	N	0.481520094	None	None	I
E/C	0.9267	likely_pathogenic	0.9445	pathogenic	-0.429	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	I
E/D	0.9006	likely_pathogenic	0.9221	pathogenic	-1.366	Destabilizing	0.974	D	0.459	neutral	N	0.521566946	None	None	I
E/F	0.9735	likely_pathogenic	0.9832	pathogenic	-0.957	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	I
E/G	0.7537	likely_pathogenic	0.8233	pathogenic	-0.941	Destabilizing	1.0	D	0.765	deleterious	N	0.510046057	None	None	I
E/H	0.934	likely_pathogenic	0.9522	pathogenic	-1.212	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	I
E/I	0.636	likely_pathogenic	0.7022	pathogenic	0.183	Stabilizing	0.999	D	0.887	deleterious	None	None	None	None	I
E/K	0.5762	likely_pathogenic	0.671	pathogenic	-0.536	Destabilizing	0.998	D	0.538	neutral	N	0.479571538	None	None	I
E/L	0.872	likely_pathogenic	0.9135	pathogenic	0.183	Stabilizing	0.999	D	0.861	deleterious	None	None	None	None	I
E/M	0.7441	likely_pathogenic	0.8045	pathogenic	0.664	Stabilizing	0.999	D	0.835	deleterious	None	None	None	None	I
E/N	0.9178	likely_pathogenic	0.9367	pathogenic	-0.819	Destabilizing	0.998	D	0.737	prob.delet.	None	None	None	None	I
E/P	0.9988	likely_pathogenic	0.9992	pathogenic	-0.067	Destabilizing	0.994	D	0.83	deleterious	None	None	None	None	I
E/Q	0.2891	likely_benign	0.3396	benign	-0.72	Destabilizing	0.999	D	0.62	neutral	N	0.484571514	None	None	I
E/R	0.7336	likely_pathogenic	0.7975	pathogenic	-0.579	Destabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	I
E/S	0.6694	likely_pathogenic	0.7252	pathogenic	-1.181	Destabilizing	0.997	D	0.597	neutral	None	None	None	None	I
E/T	0.6763	likely_pathogenic	0.7358	pathogenic	-0.908	Destabilizing	0.999	D	0.815	deleterious	None	None	None	None	I
E/V	0.3434	ambiguous	0.4062	ambiguous	-0.067	Destabilizing	0.998	D	0.829	deleterious	N	0.448303854	None	None	I
E/W	0.995	likely_pathogenic	0.9966	pathogenic	-1.071	Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	I
E/Y	0.9724	likely_pathogenic	0.9807	pathogenic	-0.755	Destabilizing	1.0	D	0.85	deleterious	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.