TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31343	94252;94253;94254	chr2:178547599;178547598;178547597	chr2:179412326;179412325;179412324
N2AB	29702	89329;89330;89331	chr2:178547599;178547598;178547597	chr2:179412326;179412325;179412324
N2A	28775	86548;86549;86550	chr2:178547599;178547598;178547597	chr2:179412326;179412325;179412324
N2B	22278	67057;67058;67059	chr2:178547599;178547598;178547597	chr2:179412326;179412325;179412324
Novex-1	22403	67432;67433;67434	chr2:178547599;178547598;178547597	chr2:179412326;179412325;179412324
Novex-2	22470	67633;67634;67635	chr2:178547599;178547598;178547597	chr2:179412326;179412325;179412324
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-116
• Domain position: 36
• Structural Position: 37
• Q(SASA): 0.1852
• 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/D	None	None	0.999	N	0.578	0.486	0.300784259202	gnomAD-4.0.0	1.59111E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85799E-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
N/A	0.7837	likely_pathogenic	0.7246	pathogenic	-1.303	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
N/C	0.5689	likely_pathogenic	0.5407	ambiguous	-0.848	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
N/D	0.8264	likely_pathogenic	0.7619	pathogenic	-1.977	Destabilizing	0.999	D	0.578	neutral	N	0.481408417	None	None	N
N/E	0.9822	likely_pathogenic	0.9726	pathogenic	-1.808	Destabilizing	0.999	D	0.658	neutral	None	None	None	None	N
N/F	0.9832	likely_pathogenic	0.9803	pathogenic	-1.087	Destabilizing	1.0	D	0.876	deleterious	None	None	None	None	N
N/G	0.5863	likely_pathogenic	0.465	ambiguous	-1.62	Destabilizing	0.999	D	0.537	neutral	None	None	None	None	N
N/H	0.4646	ambiguous	0.3874	ambiguous	-1.106	Destabilizing	1.0	D	0.679	prob.neutral	N	0.502261343	None	None	N
N/I	0.9787	likely_pathogenic	0.9802	pathogenic	-0.477	Destabilizing	1.0	D	0.885	deleterious	N	0.505134986	None	None	N
N/K	0.9745	likely_pathogenic	0.9632	pathogenic	-0.439	Destabilizing	1.0	D	0.688	prob.neutral	N	0.465061681	None	None	N
N/L	0.9433	likely_pathogenic	0.9331	pathogenic	-0.477	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
N/M	0.9649	likely_pathogenic	0.9606	pathogenic	-0.197	Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	N
N/P	0.9952	likely_pathogenic	0.9952	pathogenic	-0.728	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
N/Q	0.9352	likely_pathogenic	0.9047	pathogenic	-1.271	Destabilizing	1.0	D	0.694	prob.neutral	None	None	None	None	N
N/R	0.9374	likely_pathogenic	0.914	pathogenic	-0.333	Destabilizing	1.0	D	0.698	prob.neutral	None	None	None	None	N
N/S	0.1628	likely_benign	0.1414	benign	-1.316	Destabilizing	0.999	D	0.543	neutral	N	0.508416524	None	None	N
N/T	0.7925	likely_pathogenic	0.7673	pathogenic	-0.981	Destabilizing	0.999	D	0.645	neutral	N	0.485763283	None	None	N
N/V	0.9536	likely_pathogenic	0.9534	pathogenic	-0.728	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
N/W	0.9911	likely_pathogenic	0.9894	pathogenic	-0.892	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
N/Y	0.8123	likely_pathogenic	0.7911	pathogenic	-0.587	Destabilizing	1.0	D	0.862	deleterious	N	0.469153512	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.