TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24531	73816;73817;73818	chr2:178572541;178572540;178572539	chr2:179437268;179437267;179437266
N2AB	22890	68893;68894;68895	chr2:178572541;178572540;178572539	chr2:179437268;179437267;179437266
N2A	21963	66112;66113;66114	chr2:178572541;178572540;178572539	chr2:179437268;179437267;179437266
N2B	15466	46621;46622;46623	chr2:178572541;178572540;178572539	chr2:179437268;179437267;179437266
Novex-1	15591	46996;46997;46998	chr2:178572541;178572540;178572539	chr2:179437268;179437267;179437266
Novex-2	15658	47197;47198;47199	chr2:178572541;178572540;178572539	chr2:179437268;179437267;179437266
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: Fn3-66
• Domain position: 13
• Structural Position: 15
• Q(SASA): 0.1307
• 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/D	None	None	0.688	D	0.701	0.469	0.858470133663	gnomAD-4.0.0	1.59203E-06	None	None	None	None	N	None	0	0	None	0	2.77855E-05	None	0	0	0	0	0
V/F	None	None	0.45	N	0.55	0.341	0.722108883045	gnomAD-4.0.0	2.05306E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69877E-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	0.4456	ambiguous	0.3243	benign	-1.029	Destabilizing	0.049	N	0.491	neutral	N	0.477715568	None	None	N
V/C	0.8278	likely_pathogenic	0.7724	pathogenic	-1.107	Destabilizing	0.932	D	0.542	neutral	None	None	None	None	N
V/D	0.9063	likely_pathogenic	0.7895	pathogenic	-0.587	Destabilizing	0.688	D	0.701	prob.neutral	D	0.523736674	None	None	N
V/E	0.7866	likely_pathogenic	0.658	pathogenic	-0.641	Destabilizing	0.321	N	0.647	neutral	None	None	None	None	N
V/F	0.4482	ambiguous	0.3291	benign	-1.158	Destabilizing	0.45	N	0.55	neutral	N	0.494556057	None	None	N
V/G	0.606	likely_pathogenic	0.4408	ambiguous	-1.236	Destabilizing	0.749	D	0.682	prob.neutral	N	0.516356841	None	None	N
V/H	0.9165	likely_pathogenic	0.8546	pathogenic	-0.855	Destabilizing	0.948	D	0.71	prob.delet.	None	None	None	None	N
V/I	0.0639	likely_benign	0.0659	benign	-0.593	Destabilizing	None	N	0.14	neutral	N	0.453776749	None	None	N
V/K	0.8189	likely_pathogenic	0.7114	pathogenic	-0.616	Destabilizing	0.508	D	0.655	neutral	None	None	None	None	N
V/L	0.4013	ambiguous	0.3033	benign	-0.593	Destabilizing	0.001	N	0.303	neutral	N	0.471599502	None	None	N
V/M	0.2323	likely_benign	0.1819	benign	-0.594	Destabilizing	0.437	N	0.477	neutral	None	None	None	None	N
V/N	0.7084	likely_pathogenic	0.564	pathogenic	-0.438	Destabilizing	0.318	N	0.709	prob.delet.	None	None	None	None	N
V/P	0.9307	likely_pathogenic	0.8797	pathogenic	-0.704	Destabilizing	0.318	N	0.651	neutral	None	None	None	None	N
V/Q	0.7405	likely_pathogenic	0.6359	pathogenic	-0.679	Destabilizing	0.69	D	0.662	neutral	None	None	None	None	N
V/R	0.8143	likely_pathogenic	0.6911	pathogenic	-0.213	Destabilizing	0.688	D	0.705	prob.neutral	None	None	None	None	N
V/S	0.5778	likely_pathogenic	0.4454	ambiguous	-0.956	Destabilizing	0.543	D	0.557	neutral	None	None	None	None	N
V/T	0.3501	ambiguous	0.2926	benign	-0.902	Destabilizing	0.063	N	0.449	neutral	None	None	None	None	N
V/W	0.959	likely_pathogenic	0.917	pathogenic	-1.217	Destabilizing	0.985	D	0.713	prob.delet.	None	None	None	None	N
V/Y	0.8322	likely_pathogenic	0.7259	pathogenic	-0.873	Destabilizing	0.688	D	0.554	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.