TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27807	83644;83645;83646	chr2:178562713;178562712;178562711	chr2:179427440;179427439;179427438
N2AB	26166	78721;78722;78723	chr2:178562713;178562712;178562711	chr2:179427440;179427439;179427438
N2A	25239	75940;75941;75942	chr2:178562713;178562712;178562711	chr2:179427440;179427439;179427438
N2B	18742	56449;56450;56451	chr2:178562713;178562712;178562711	chr2:179427440;179427439;179427438
Novex-1	18867	56824;56825;56826	chr2:178562713;178562712;178562711	chr2:179427440;179427439;179427438
Novex-2	18934	57025;57026;57027	chr2:178562713;178562712;178562711	chr2:179427440;179427439;179427438
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-90
• Domain position: 42
• Structural Position: 44
• Q(SASA): 0.1796
• 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	0.986	N	0.628	0.563	0.485634191555	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.9375E-06	0	0
E/Q	rs1439000157	-1.067	0.99	N	0.543	0.251	0.411932830014	gnomAD-2.1.1	4.23E-06	None	None	None	None	N	None	0	3.13E-05	None	0	0	None	0	None	0	0	0
E/Q	rs1439000157	-1.067	0.99	N	0.543	0.251	0.411932830014	gnomAD-4.0.0	1.63494E-06	None	None	None	None	N	None	0	2.4505E-05	None	0	0	None	0	0	0	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	0.7921	likely_pathogenic	0.8169	pathogenic	-1.007	Destabilizing	0.914	D	0.511	neutral	N	0.487550936	None	None	N
E/C	0.9914	likely_pathogenic	0.9924	pathogenic	-0.535	Destabilizing	1.0	D	0.74	deleterious	None	None	None	None	N
E/D	0.4593	ambiguous	0.4931	ambiguous	-1.183	Destabilizing	0.008	N	0.32	neutral	N	0.49674088	None	None	N
E/F	0.9931	likely_pathogenic	0.9945	pathogenic	-0.459	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
E/G	0.8371	likely_pathogenic	0.856	pathogenic	-1.375	Destabilizing	0.986	D	0.628	neutral	N	0.490704488	None	None	N
E/H	0.9748	likely_pathogenic	0.9813	pathogenic	-0.738	Destabilizing	0.999	D	0.61	neutral	None	None	None	None	N
E/I	0.9609	likely_pathogenic	0.969	pathogenic	0.002	Stabilizing	0.994	D	0.817	deleterious	None	None	None	None	N
E/K	0.8957	likely_pathogenic	0.921	pathogenic	-0.766	Destabilizing	0.109	N	0.333	neutral	N	0.47145769	None	None	N
E/L	0.9294	likely_pathogenic	0.9459	pathogenic	0.002	Stabilizing	0.988	D	0.751	deleterious	None	None	None	None	N
E/M	0.9497	likely_pathogenic	0.9586	pathogenic	0.526	Stabilizing	0.997	D	0.736	prob.delet.	None	None	None	None	N
E/N	0.9032	likely_pathogenic	0.9188	pathogenic	-1.225	Destabilizing	0.975	D	0.578	neutral	None	None	None	None	N
E/P	0.9707	likely_pathogenic	0.9703	pathogenic	-0.314	Destabilizing	0.963	D	0.737	prob.delet.	None	None	None	None	N
E/Q	0.7409	likely_pathogenic	0.7768	pathogenic	-1.094	Destabilizing	0.99	D	0.543	neutral	N	0.484624421	None	None	N
E/R	0.9487	likely_pathogenic	0.9596	pathogenic	-0.465	Destabilizing	0.989	D	0.568	neutral	None	None	None	None	N
E/S	0.8929	likely_pathogenic	0.9085	pathogenic	-1.555	Destabilizing	0.966	D	0.443	neutral	None	None	None	None	N
E/T	0.9445	likely_pathogenic	0.9516	pathogenic	-1.25	Destabilizing	0.993	D	0.633	neutral	None	None	None	None	N
E/V	0.9022	likely_pathogenic	0.9172	pathogenic	-0.314	Destabilizing	0.979	D	0.719	prob.delet.	N	0.505517061	None	None	N
E/W	0.9977	likely_pathogenic	0.9983	pathogenic	-0.194	Destabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	N
E/Y	0.9859	likely_pathogenic	0.9895	pathogenic	-0.212	Destabilizing	1.0	D	0.771	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.