TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24669	74230;74231;74232	chr2:178572127;178572126;178572125	chr2:179436854;179436853;179436852
N2AB	23028	69307;69308;69309	chr2:178572127;178572126;178572125	chr2:179436854;179436853;179436852
N2A	22101	66526;66527;66528	chr2:178572127;178572126;178572125	chr2:179436854;179436853;179436852
N2B	15604	47035;47036;47037	chr2:178572127;178572126;178572125	chr2:179436854;179436853;179436852
Novex-1	15729	47410;47411;47412	chr2:178572127;178572126;178572125	chr2:179436854;179436853;179436852
Novex-2	15796	47611;47612;47613	chr2:178572127;178572126;178572125	chr2:179436854;179436853;179436852
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Fn3-67
• Domain position: 54
• Structural Position: 77
• Q(SASA): 0.1431
• 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/I	rs768046818	None	0.484	N	0.533	0.207	0.544303689236	gnomAD-4.0.0	1.02665E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.34945E-05	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	0.3133	likely_benign	0.2788	benign	-1.322	Destabilizing	0.555	D	0.504	neutral	N	0.474545109	None	None	N
V/C	0.8212	likely_pathogenic	0.7906	pathogenic	-0.788	Destabilizing	0.998	D	0.627	neutral	None	None	None	None	N
V/D	0.905	likely_pathogenic	0.8826	pathogenic	-1.294	Destabilizing	0.981	D	0.693	prob.neutral	N	0.491128427	None	None	N
V/E	0.7998	likely_pathogenic	0.768	pathogenic	-1.172	Destabilizing	0.958	D	0.615	neutral	None	None	None	None	N
V/F	0.568	likely_pathogenic	0.5312	ambiguous	-0.743	Destabilizing	0.996	D	0.658	neutral	N	0.494170301	None	None	N
V/G	0.42	ambiguous	0.3776	ambiguous	-1.754	Destabilizing	0.059	N	0.445	neutral	N	0.471342331	None	None	N
V/H	0.9326	likely_pathogenic	0.9173	pathogenic	-1.419	Destabilizing	0.999	D	0.719	prob.delet.	None	None	None	None	N
V/I	0.1495	likely_benign	0.1397	benign	-0.189	Destabilizing	0.484	N	0.533	neutral	N	0.49281514	None	None	N
V/K	0.8454	likely_pathogenic	0.8203	pathogenic	-1.057	Destabilizing	0.961	D	0.629	neutral	None	None	None	None	N
V/L	0.5116	ambiguous	0.4885	ambiguous	-0.189	Destabilizing	0.279	N	0.54	neutral	N	0.474825051	None	None	N
V/M	0.3285	likely_benign	0.298	benign	-0.18	Destabilizing	0.996	D	0.593	neutral	None	None	None	None	N
V/N	0.7089	likely_pathogenic	0.6536	pathogenic	-1.117	Destabilizing	0.784	D	0.7	prob.neutral	None	None	None	None	N
V/P	0.9724	likely_pathogenic	0.9639	pathogenic	-0.533	Destabilizing	0.957	D	0.676	prob.neutral	None	None	None	None	N
V/Q	0.7522	likely_pathogenic	0.7138	pathogenic	-1.084	Destabilizing	0.991	D	0.691	prob.neutral	None	None	None	None	N
V/R	0.8182	likely_pathogenic	0.7895	pathogenic	-0.809	Destabilizing	0.991	D	0.722	prob.delet.	None	None	None	None	N
V/S	0.3632	ambiguous	0.3174	benign	-1.706	Destabilizing	0.8	D	0.611	neutral	None	None	None	None	N
V/T	0.2558	likely_benign	0.2278	benign	-1.456	Destabilizing	0.041	N	0.331	neutral	None	None	None	None	N
V/W	0.9874	likely_pathogenic	0.9827	pathogenic	-1.148	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
V/Y	0.931	likely_pathogenic	0.9145	pathogenic	-0.725	Destabilizing	0.997	D	0.654	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.