TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1480	4663;4664;4665	chr2:178777746;178777745;178777744	chr2:179642473;179642472;179642471
N2AB	1480	4663;4664;4665	chr2:178777746;178777745;178777744	chr2:179642473;179642472;179642471
N2A	1480	4663;4664;4665	chr2:178777746;178777745;178777744	chr2:179642473;179642472;179642471
N2B	1434	4525;4526;4527	chr2:178777746;178777745;178777744	chr2:179642473;179642472;179642471
Novex-1	1434	4525;4526;4527	chr2:178777746;178777745;178777744	chr2:179642473;179642472;179642471
Novex-2	1434	4525;4526;4527	chr2:178777746;178777745;178777744	chr2:179642473;179642472;179642471
Novex-3	1480	4663;4664;4665	chr2:178777746;178777745;178777744	chr2:179642473;179642472;179642471

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-6
• Domain position: 24
• Structural Position: 35
• Q(SASA): 0.1223
• 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
V/A	None	None	0.999	D	0.601	0.61	0.746554498716	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-06	0	0
V/L	None	None	0.997	D	0.627	0.55	0.689064770846	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
V/A	0.8169	likely_pathogenic	0.8128	pathogenic	-2.099	Highly Destabilizing	0.999	D	0.601	neutral	D	0.532459561	None	None	N
V/C	0.9833	likely_pathogenic	0.9833	pathogenic	-1.647	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
V/D	0.9985	likely_pathogenic	0.9986	pathogenic	-2.777	Highly Destabilizing	1.0	D	0.846	deleterious	D	0.810871032	None	None	N
V/E	0.9949	likely_pathogenic	0.9947	pathogenic	-2.568	Highly Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
V/F	0.9666	likely_pathogenic	0.9667	pathogenic	-1.153	Destabilizing	1.0	D	0.843	deleterious	D	0.657360819	None	None	N
V/G	0.941	likely_pathogenic	0.9415	pathogenic	-2.618	Highly Destabilizing	1.0	D	0.84	deleterious	D	0.738637061	None	None	N
V/H	0.9993	likely_pathogenic	0.9993	pathogenic	-2.354	Highly Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
V/I	0.2191	likely_benign	0.2104	benign	-0.65	Destabilizing	0.997	D	0.542	neutral	D	0.561997815	None	None	N
V/K	0.9983	likely_pathogenic	0.9981	pathogenic	-1.728	Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
V/L	0.9003	likely_pathogenic	0.8951	pathogenic	-0.65	Destabilizing	0.997	D	0.627	neutral	D	0.649022803	None	None	N
V/M	0.8876	likely_pathogenic	0.8774	pathogenic	-0.784	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
V/N	0.9953	likely_pathogenic	0.9953	pathogenic	-2.019	Highly Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
V/P	0.9958	likely_pathogenic	0.9952	pathogenic	-1.107	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
V/Q	0.9965	likely_pathogenic	0.9962	pathogenic	-1.878	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
V/R	0.9962	likely_pathogenic	0.9961	pathogenic	-1.544	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
V/S	0.9606	likely_pathogenic	0.9594	pathogenic	-2.604	Highly Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	N
V/T	0.8728	likely_pathogenic	0.8636	pathogenic	-2.264	Highly Destabilizing	0.999	D	0.627	neutral	None	None	None	None	N
V/W	0.9995	likely_pathogenic	0.9995	pathogenic	-1.687	Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
V/Y	0.9966	likely_pathogenic	0.9966	pathogenic	-1.331	Destabilizing	1.0	D	0.847	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.