TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27813	83662;83663;83664	chr2:178562695;178562694;178562693	chr2:179427422;179427421;179427420
N2AB	26172	78739;78740;78741	chr2:178562695;178562694;178562693	chr2:179427422;179427421;179427420
N2A	25245	75958;75959;75960	chr2:178562695;178562694;178562693	chr2:179427422;179427421;179427420
N2B	18748	56467;56468;56469	chr2:178562695;178562694;178562693	chr2:179427422;179427421;179427420
Novex-1	18873	56842;56843;56844	chr2:178562695;178562694;178562693	chr2:179427422;179427421;179427420
Novex-2	18940	57043;57044;57045	chr2:178562695;178562694;178562693	chr2:179427422;179427421;179427420
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-90
• Domain position: 48
• Structural Position: 65
• Q(SASA): 0.2487
• 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
Y/C	None	None	1.0	N	0.509	0.36	0.503248607038	gnomAD-4.0.0	1.63898E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.91937E-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
Y/A	0.9779	likely_pathogenic	0.9766	pathogenic	-2.695	Highly Destabilizing	0.988	D	0.433	neutral	None	None	None	None	N
Y/C	0.7995	likely_pathogenic	0.8129	pathogenic	-1.1	Destabilizing	1.0	D	0.509	neutral	N	0.489638762	None	None	N
Y/D	0.9825	likely_pathogenic	0.9817	pathogenic	-1.395	Destabilizing	0.998	D	0.547	neutral	N	0.468629625	None	None	N
Y/E	0.9977	likely_pathogenic	0.9974	pathogenic	-1.316	Destabilizing	0.996	D	0.497	neutral	None	None	None	None	N
Y/F	0.0918	likely_benign	0.0908	benign	-1.298	Destabilizing	0.005	N	0.116	neutral	N	0.445637269	None	None	N
Y/G	0.9782	likely_pathogenic	0.9772	pathogenic	-3.0	Highly Destabilizing	0.988	D	0.449	neutral	None	None	None	None	N
Y/H	0.8338	likely_pathogenic	0.8209	pathogenic	-1.212	Destabilizing	0.995	D	0.485	neutral	N	0.485634698	None	None	N
Y/I	0.9718	likely_pathogenic	0.9683	pathogenic	-1.757	Destabilizing	0.606	D	0.397	neutral	None	None	None	None	N
Y/K	0.9969	likely_pathogenic	0.9966	pathogenic	-1.309	Destabilizing	0.972	D	0.509	neutral	None	None	None	None	N
Y/L	0.9378	likely_pathogenic	0.9334	pathogenic	-1.757	Destabilizing	0.241	N	0.437	neutral	None	None	None	None	N
Y/M	0.9688	likely_pathogenic	0.9646	pathogenic	-1.313	Destabilizing	0.996	D	0.475	neutral	None	None	None	None	N
Y/N	0.9359	likely_pathogenic	0.9252	pathogenic	-1.57	Destabilizing	0.998	D	0.529	neutral	N	0.46531517	None	None	N
Y/P	0.9876	likely_pathogenic	0.9846	pathogenic	-2.068	Highly Destabilizing	0.999	D	0.544	neutral	None	None	None	None	N
Y/Q	0.994	likely_pathogenic	0.9937	pathogenic	-1.598	Destabilizing	0.996	D	0.476	neutral	None	None	None	None	N
Y/R	0.9893	likely_pathogenic	0.9886	pathogenic	-0.689	Destabilizing	0.992	D	0.529	neutral	None	None	None	None	N
Y/S	0.9285	likely_pathogenic	0.9254	pathogenic	-2.12	Highly Destabilizing	0.995	D	0.479	neutral	N	0.472503966	None	None	N
Y/T	0.9844	likely_pathogenic	0.9828	pathogenic	-1.954	Destabilizing	0.996	D	0.476	neutral	None	None	None	None	N
Y/V	0.9459	likely_pathogenic	0.9421	pathogenic	-2.068	Highly Destabilizing	0.975	D	0.385	neutral	None	None	None	None	N
Y/W	0.2901	likely_benign	0.2888	benign	-0.774	Destabilizing	0.138	N	0.257	neutral	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.