TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2691	8296;8297;8298	chr2:178771256;178771255;178771254	chr2:179635983;179635982;179635981
N2AB	2691	8296;8297;8298	chr2:178771256;178771255;178771254	chr2:179635983;179635982;179635981
N2A	2691	8296;8297;8298	chr2:178771256;178771255;178771254	chr2:179635983;179635982;179635981
N2B	2645	8158;8159;8160	chr2:178771256;178771255;178771254	chr2:179635983;179635982;179635981
Novex-1	2645	8158;8159;8160	chr2:178771256;178771255;178771254	chr2:179635983;179635982;179635981
Novex-2	2645	8158;8159;8160	chr2:178771256;178771255;178771254	chr2:179635983;179635982;179635981
Novex-3	2691	8296;8297;8298	chr2:178771256;178771255;178771254	chr2:179635983;179635982;179635981

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-16
• Domain position: 71
• Structural Position: 156
• Q(SASA): 0.0805
• 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
Y/D	rs1257930872	None	0.916	N	0.862	0.456	0.482209950775	gnomAD-4.0.0	3.18125E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71318E-06	0	0
Y/H	None	None	0.916	N	0.686	0.4	0.272205846399	gnomAD-4.0.0	1.59062E-06	None	None	None	None	N	None	0	2.28686E-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
Y/A	0.9744	likely_pathogenic	0.9698	pathogenic	-3.142	Highly Destabilizing	0.399	N	0.819	deleterious	None	None	None	None	N
Y/C	0.4857	ambiguous	0.4726	ambiguous	-1.493	Destabilizing	0.976	D	0.831	deleterious	N	0.280051257	None	None	N
Y/D	0.9946	likely_pathogenic	0.9928	pathogenic	-3.498	Highly Destabilizing	0.916	D	0.862	deleterious	N	0.362149426	None	None	N
Y/E	0.9968	likely_pathogenic	0.996	pathogenic	-3.279	Highly Destabilizing	0.826	D	0.857	deleterious	None	None	None	None	N
Y/F	0.133	likely_benign	0.1317	benign	-1.197	Destabilizing	0.002	N	0.367	neutral	N	0.346163504	None	None	N
Y/G	0.9711	likely_pathogenic	0.9658	pathogenic	-3.555	Highly Destabilizing	0.826	D	0.857	deleterious	None	None	None	None	N
Y/H	0.9232	likely_pathogenic	0.9122	pathogenic	-2.258	Highly Destabilizing	0.916	D	0.686	prob.neutral	N	0.362149426	None	None	N
Y/I	0.9266	likely_pathogenic	0.9131	pathogenic	-1.754	Destabilizing	0.539	D	0.777	deleterious	None	None	None	None	N
Y/K	0.9968	likely_pathogenic	0.9958	pathogenic	-2.178	Highly Destabilizing	0.826	D	0.857	deleterious	None	None	None	None	N
Y/L	0.8271	likely_pathogenic	0.8058	pathogenic	-1.754	Destabilizing	0.25	N	0.725	prob.delet.	None	None	None	None	N
Y/M	0.9463	likely_pathogenic	0.9363	pathogenic	-1.368	Destabilizing	0.947	D	0.761	deleterious	None	None	None	None	N
Y/N	0.9676	likely_pathogenic	0.956	pathogenic	-3.001	Highly Destabilizing	0.916	D	0.842	deleterious	N	0.362149426	None	None	N
Y/P	0.9984	likely_pathogenic	0.9982	pathogenic	-2.235	Highly Destabilizing	0.935	D	0.867	deleterious	None	None	None	None	N
Y/Q	0.9934	likely_pathogenic	0.9919	pathogenic	-2.721	Highly Destabilizing	0.935	D	0.763	deleterious	None	None	None	None	N
Y/R	0.9864	likely_pathogenic	0.9835	pathogenic	-2.028	Highly Destabilizing	0.826	D	0.845	deleterious	None	None	None	None	N
Y/S	0.9577	likely_pathogenic	0.9466	pathogenic	-3.301	Highly Destabilizing	0.781	D	0.853	deleterious	N	0.362149426	None	None	N
Y/T	0.9878	likely_pathogenic	0.9847	pathogenic	-2.962	Highly Destabilizing	0.826	D	0.851	deleterious	None	None	None	None	N
Y/V	0.852	likely_pathogenic	0.8278	pathogenic	-2.235	Highly Destabilizing	0.25	N	0.763	deleterious	None	None	None	None	N
Y/W	0.6788	likely_pathogenic	0.6974	pathogenic	-0.463	Destabilizing	0.947	D	0.681	prob.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.