TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29549	88870;88871;88872	chr2:178554702;178554701;178554700	chr2:179419429;179419428;179419427
N2AB	27908	83947;83948;83949	chr2:178554702;178554701;178554700	chr2:179419429;179419428;179419427
N2A	26981	81166;81167;81168	chr2:178554702;178554701;178554700	chr2:179419429;179419428;179419427
N2B	20484	61675;61676;61677	chr2:178554702;178554701;178554700	chr2:179419429;179419428;179419427
Novex-1	20609	62050;62051;62052	chr2:178554702;178554701;178554700	chr2:179419429;179419428;179419427
Novex-2	20676	62251;62252;62253	chr2:178554702;178554701;178554700	chr2:179419429;179419428;179419427
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: Fn3-103
• Domain position: 17
• Structural Position: 18
• Q(SASA): 0.7339
• 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	rs779704459	-1.12	0.722	N	0.491	0.24	0.287603790349	gnomAD-2.1.1	1.07E-05	None	None	None	None	N	None	8.26E-05	0	None	0	0	None	0	None	0	7.81E-06	0
E/G	rs779704459	-1.12	0.722	N	0.491	0.24	0.287603790349	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	1.47E-05	0	0
E/G	rs779704459	-1.12	0.722	N	0.491	0.24	0.287603790349	gnomAD-4.0.0	6.19665E-06	None	None	None	None	N	None	4.0062E-05	0	None	0	0	None	0	0	5.93289E-06	0	0
E/K	None	None	0.722	N	0.517	0.256	0.200317383148	gnomAD-4.0.0	3.42089E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.49711E-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	0.658	likely_pathogenic	0.5649	pathogenic	-0.389	Destabilizing	0.565	D	0.485	neutral	N	0.506128367	None	None	N
E/C	0.9864	likely_pathogenic	0.9807	pathogenic	-0.096	Destabilizing	0.996	D	0.543	neutral	None	None	None	None	N
E/D	0.2947	likely_benign	0.2406	benign	-0.352	Destabilizing	0.003	N	0.105	neutral	N	0.400787626	None	None	N
E/F	0.988	likely_pathogenic	0.9827	pathogenic	-0.243	Destabilizing	0.961	D	0.515	neutral	None	None	None	None	N
E/G	0.4753	ambiguous	0.3961	ambiguous	-0.586	Destabilizing	0.722	D	0.491	neutral	N	0.486118454	None	None	N
E/H	0.9205	likely_pathogenic	0.893	pathogenic	0.025	Stabilizing	0.987	D	0.438	neutral	None	None	None	None	N
E/I	0.9565	likely_pathogenic	0.9316	pathogenic	0.095	Stabilizing	0.858	D	0.513	neutral	None	None	None	None	N
E/K	0.6774	likely_pathogenic	0.5953	pathogenic	0.291	Stabilizing	0.722	D	0.517	neutral	N	0.491870991	None	None	N
E/L	0.9296	likely_pathogenic	0.8978	pathogenic	0.095	Stabilizing	0.633	D	0.471	neutral	None	None	None	None	N
E/M	0.9364	likely_pathogenic	0.9082	pathogenic	0.16	Stabilizing	0.989	D	0.469	neutral	None	None	None	None	N
E/N	0.6723	likely_pathogenic	0.5701	pathogenic	-0.047	Destabilizing	0.775	D	0.491	neutral	None	None	None	None	N
E/P	0.9889	likely_pathogenic	0.9854	pathogenic	-0.047	Destabilizing	0.961	D	0.463	neutral	None	None	None	None	N
E/Q	0.4761	ambiguous	0.4108	ambiguous	-0.012	Destabilizing	0.84	D	0.493	neutral	N	0.502087984	None	None	N
E/R	0.8022	likely_pathogenic	0.7456	pathogenic	0.52	Stabilizing	0.923	D	0.467	neutral	None	None	None	None	N
E/S	0.6085	likely_pathogenic	0.5217	ambiguous	-0.209	Destabilizing	0.633	D	0.476	neutral	None	None	None	None	N
E/T	0.7208	likely_pathogenic	0.5875	pathogenic	-0.047	Destabilizing	0.011	N	0.247	neutral	None	None	None	None	N
E/V	0.8748	likely_pathogenic	0.811	pathogenic	-0.047	Destabilizing	0.565	D	0.459	neutral	N	0.477293813	None	None	N
E/W	0.9927	likely_pathogenic	0.9903	pathogenic	-0.084	Destabilizing	0.996	D	0.647	neutral	None	None	None	None	N
E/Y	0.9725	likely_pathogenic	0.9597	pathogenic	0.001	Stabilizing	0.987	D	0.485	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.