TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20642	62149;62150;62151	chr2:178589801;178589800;178589799	chr2:179454528;179454527;179454526
N2AB	19001	57226;57227;57228	chr2:178589801;178589800;178589799	chr2:179454528;179454527;179454526
N2A	18074	54445;54446;54447	chr2:178589801;178589800;178589799	chr2:179454528;179454527;179454526
N2B	11577	34954;34955;34956	chr2:178589801;178589800;178589799	chr2:179454528;179454527;179454526
Novex-1	11702	35329;35330;35331	chr2:178589801;178589800;178589799	chr2:179454528;179454527;179454526
Novex-2	11769	35530;35531;35532	chr2:178589801;178589800;178589799	chr2:179454528;179454527;179454526
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-37
• Domain position: 74
• Structural Position: 108
• Q(SASA): 0.0735
• 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/L	None	None	0.997	D	0.655	0.596	0.790187556284	gnomAD-4.0.0	1.59177E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.88232E-05	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
V/A	0.931	likely_pathogenic	0.9142	pathogenic	-2.336	Highly Destabilizing	0.999	D	0.646	neutral	D	0.569267023	None	None	N
V/C	0.9743	likely_pathogenic	0.969	pathogenic	-1.799	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	N
V/D	0.9991	likely_pathogenic	0.9986	pathogenic	-3.417	Highly Destabilizing	1.0	D	0.879	deleterious	D	0.631805312	None	None	N
V/E	0.9974	likely_pathogenic	0.9961	pathogenic	-3.141	Highly Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	N
V/F	0.9661	likely_pathogenic	0.9504	pathogenic	-1.337	Destabilizing	1.0	D	0.798	deleterious	D	0.551162768	None	None	N
V/G	0.9621	likely_pathogenic	0.9464	pathogenic	-2.885	Highly Destabilizing	1.0	D	0.869	deleterious	D	0.631805312	None	None	N
V/H	0.9994	likely_pathogenic	0.999	pathogenic	-2.777	Highly Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
V/I	0.1383	likely_benign	0.1298	benign	-0.751	Destabilizing	0.997	D	0.612	neutral	D	0.53689207	None	None	N
V/K	0.998	likely_pathogenic	0.997	pathogenic	-2.012	Highly Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	N
V/L	0.8674	likely_pathogenic	0.8215	pathogenic	-0.751	Destabilizing	0.997	D	0.655	neutral	D	0.529002681	None	None	N
V/M	0.9303	likely_pathogenic	0.9102	pathogenic	-0.921	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
V/N	0.9969	likely_pathogenic	0.9949	pathogenic	-2.557	Highly Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
V/P	0.9984	likely_pathogenic	0.9973	pathogenic	-1.26	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
V/Q	0.9971	likely_pathogenic	0.996	pathogenic	-2.292	Highly Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
V/R	0.9955	likely_pathogenic	0.9934	pathogenic	-1.93	Destabilizing	1.0	D	0.894	deleterious	None	None	None	None	N
V/S	0.9846	likely_pathogenic	0.9791	pathogenic	-3.042	Highly Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
V/T	0.9521	likely_pathogenic	0.9479	pathogenic	-2.634	Highly Destabilizing	0.999	D	0.667	neutral	None	None	None	None	N
V/W	0.9996	likely_pathogenic	0.9994	pathogenic	-1.986	Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
V/Y	0.9967	likely_pathogenic	0.9948	pathogenic	-1.64	Destabilizing	1.0	D	0.808	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.