TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2799	8620;8621;8622	chr2:178770306;178770305;178770304	chr2:179635033;179635032;179635031
N2AB	2799	8620;8621;8622	chr2:178770306;178770305;178770304	chr2:179635033;179635032;179635031
N2A	2799	8620;8621;8622	chr2:178770306;178770305;178770304	chr2:179635033;179635032;179635031
N2B	2753	8482;8483;8484	chr2:178770306;178770305;178770304	chr2:179635033;179635032;179635031
Novex-1	2753	8482;8483;8484	chr2:178770306;178770305;178770304	chr2:179635033;179635032;179635031
Novex-2	2753	8482;8483;8484	chr2:178770306;178770305;178770304	chr2:179635033;179635032;179635031
Novex-3	2799	8620;8621;8622	chr2:178770306;178770305;178770304	chr2:179635033;179635032;179635031

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-18
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.2007
• 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
K/I	None	None	0.013	D	0.445	0.352	0.61907107664	gnomAD-4.0.0	6.84062E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99287E-07	0	0
K/Q	None	None	0.975	N	0.697	0.317	0.361558571881	gnomAD-4.0.0	1.59047E-06	None	None	None	None	N	None	0	0	None	0	2.77331E-05	None	0	0	0	0	0
K/R	None	None	0.787	N	0.583	0.244	0.401042353794	gnomAD-4.0.0	6.84062E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99287E-07	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
K/A	0.9618	likely_pathogenic	0.9668	pathogenic	-0.354	Destabilizing	0.707	D	0.595	neutral	None	None	None	None	N
K/C	0.9657	likely_pathogenic	0.9677	pathogenic	-0.492	Destabilizing	0.995	D	0.695	prob.neutral	None	None	None	None	N
K/D	0.9898	likely_pathogenic	0.9896	pathogenic	0.113	Stabilizing	0.945	D	0.734	prob.delet.	None	None	None	None	N
K/E	0.9072	likely_pathogenic	0.9199	pathogenic	0.219	Stabilizing	0.787	D	0.583	neutral	D	0.554338975	None	None	N
K/F	0.9942	likely_pathogenic	0.9945	pathogenic	-0.017	Destabilizing	0.894	D	0.728	prob.delet.	None	None	None	None	N
K/G	0.9647	likely_pathogenic	0.9644	pathogenic	-0.703	Destabilizing	0.945	D	0.633	neutral	None	None	None	None	N
K/H	0.7927	likely_pathogenic	0.8119	pathogenic	-0.912	Destabilizing	0.995	D	0.706	prob.neutral	None	None	None	None	N
K/I	0.9636	likely_pathogenic	0.9687	pathogenic	0.538	Stabilizing	0.013	N	0.445	neutral	D	0.637724439	None	None	N
K/L	0.9391	likely_pathogenic	0.9456	pathogenic	0.538	Stabilizing	0.293	N	0.549	neutral	None	None	None	None	N
K/M	0.9023	likely_pathogenic	0.9153	pathogenic	0.227	Stabilizing	0.97	D	0.711	prob.delet.	None	None	None	None	N
K/N	0.9708	likely_pathogenic	0.9735	pathogenic	-0.337	Destabilizing	0.975	D	0.697	prob.neutral	D	0.615309917	None	None	N
K/P	0.9962	likely_pathogenic	0.9962	pathogenic	0.272	Stabilizing	0.981	D	0.742	deleterious	None	None	None	None	N
K/Q	0.5489	ambiguous	0.6082	pathogenic	-0.364	Destabilizing	0.975	D	0.697	prob.neutral	N	0.503649204	None	None	N
K/R	0.12	likely_benign	0.1315	benign	-0.467	Destabilizing	0.787	D	0.583	neutral	N	0.51133554	None	None	N
K/S	0.9629	likely_pathogenic	0.9673	pathogenic	-0.955	Destabilizing	0.83	D	0.614	neutral	None	None	None	None	N
K/T	0.8943	likely_pathogenic	0.9048	pathogenic	-0.649	Destabilizing	0.864	D	0.679	prob.neutral	N	0.497064156	None	None	N
K/V	0.9364	likely_pathogenic	0.9451	pathogenic	0.272	Stabilizing	0.293	N	0.556	neutral	None	None	None	None	N
K/W	0.981	likely_pathogenic	0.9824	pathogenic	0.068	Stabilizing	0.995	D	0.714	prob.delet.	None	None	None	None	N
K/Y	0.9778	likely_pathogenic	0.9793	pathogenic	0.349	Stabilizing	0.945	D	0.715	prob.delet.	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.