TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2715	8368;8369;8370	chr2:178770649;178770648;178770647	chr2:179635376;179635375;179635374
N2AB	2715	8368;8369;8370	chr2:178770649;178770648;178770647	chr2:179635376;179635375;179635374
N2A	2715	8368;8369;8370	chr2:178770649;178770648;178770647	chr2:179635376;179635375;179635374
N2B	2669	8230;8231;8232	chr2:178770649;178770648;178770647	chr2:179635376;179635375;179635374
Novex-1	2669	8230;8231;8232	chr2:178770649;178770648;178770647	chr2:179635376;179635375;179635374
Novex-2	2669	8230;8231;8232	chr2:178770649;178770648;178770647	chr2:179635376;179635375;179635374
Novex-3	2715	8368;8369;8370	chr2:178770649;178770648;178770647	chr2:179635376;179635375;179635374

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Ig-17
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.8793
• 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
N/S	None	None	0.999	D	0.512	0.606	0.436993770938	gnomAD-4.0.0	6.84387E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99315E-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
N/A	0.9174	likely_pathogenic	0.9261	pathogenic	-0.031	Destabilizing	1.0	D	0.603	neutral	None	None	None	None	N
N/C	0.954	likely_pathogenic	0.9633	pathogenic	-0.114	Destabilizing	1.0	D	0.642	neutral	None	None	None	None	N
N/D	0.5666	likely_pathogenic	0.5276	ambiguous	0.037	Stabilizing	0.999	D	0.557	neutral	N	0.502382272	None	None	N
N/E	0.956	likely_pathogenic	0.9611	pathogenic	-0.022	Destabilizing	0.999	D	0.609	neutral	None	None	None	None	N
N/F	0.9793	likely_pathogenic	0.9851	pathogenic	-0.747	Destabilizing	1.0	D	0.606	neutral	None	None	None	None	N
N/G	0.8899	likely_pathogenic	0.8938	pathogenic	-0.086	Destabilizing	0.999	D	0.497	neutral	None	None	None	None	N
N/H	0.7017	likely_pathogenic	0.6938	pathogenic	-0.074	Destabilizing	1.0	D	0.587	neutral	D	0.655944816	None	None	N
N/I	0.9135	likely_pathogenic	0.9348	pathogenic	0.017	Stabilizing	1.0	D	0.633	neutral	D	0.655358915	None	None	N
N/K	0.968	likely_pathogenic	0.9708	pathogenic	0.033	Stabilizing	1.0	D	0.625	neutral	D	0.656736144	None	None	N
N/L	0.9009	likely_pathogenic	0.925	pathogenic	0.017	Stabilizing	1.0	D	0.631	neutral	None	None	None	None	N
N/M	0.9283	likely_pathogenic	0.9419	pathogenic	-0.149	Destabilizing	1.0	D	0.557	neutral	None	None	None	None	N
N/P	0.8968	likely_pathogenic	0.8999	pathogenic	0.021	Stabilizing	1.0	D	0.598	neutral	None	None	None	None	N
N/Q	0.9573	likely_pathogenic	0.9594	pathogenic	-0.33	Destabilizing	1.0	D	0.603	neutral	None	None	None	None	N
N/R	0.9725	likely_pathogenic	0.976	pathogenic	0.108	Stabilizing	1.0	D	0.628	neutral	None	None	None	None	N
N/S	0.4679	ambiguous	0.4522	ambiguous	-0.15	Destabilizing	0.999	D	0.512	neutral	D	0.550056684	None	None	N
N/T	0.7675	likely_pathogenic	0.7756	pathogenic	-0.108	Destabilizing	0.999	D	0.612	neutral	D	0.656848245	None	None	N
N/V	0.9268	likely_pathogenic	0.9453	pathogenic	0.021	Stabilizing	1.0	D	0.624	neutral	None	None	None	None	N
N/W	0.9935	likely_pathogenic	0.9941	pathogenic	-0.958	Destabilizing	1.0	D	0.639	neutral	None	None	None	None	N
N/Y	0.7276	likely_pathogenic	0.7718	pathogenic	-0.596	Destabilizing	1.0	D	0.58	neutral	D	0.655358915	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.