TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25489	76690;76691;76692	chr2:178569667;178569666;178569665	chr2:179434394;179434393;179434392
N2AB	23848	71767;71768;71769	chr2:178569667;178569666;178569665	chr2:179434394;179434393;179434392
N2A	22921	68986;68987;68988	chr2:178569667;178569666;178569665	chr2:179434394;179434393;179434392
N2B	16424	49495;49496;49497	chr2:178569667;178569666;178569665	chr2:179434394;179434393;179434392
Novex-1	16549	49870;49871;49872	chr2:178569667;178569666;178569665	chr2:179434394;179434393;179434392
Novex-2	16616	50071;50072;50073	chr2:178569667;178569666;178569665	chr2:179434394;179434393;179434392
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: Fn3-73
• Domain position: 85
• Structural Position: 117
• Q(SASA): 0.4117
• Predicted PPI site: I

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/G	None	None	0.967	N	0.795	0.407	0.75040067796	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.625E-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	0.1285	likely_benign	0.145	benign	-1.036	Destabilizing	0.892	D	0.639	neutral	N	0.476517536	None	None	I
V/C	0.6634	likely_pathogenic	0.7025	pathogenic	-0.808	Destabilizing	0.999	D	0.811	deleterious	None	None	None	None	I
V/D	0.4696	ambiguous	0.5371	ambiguous	-0.482	Destabilizing	0.935	D	0.798	deleterious	N	0.468633306	None	None	I
V/E	0.307	likely_benign	0.372	ambiguous	-0.552	Destabilizing	0.073	N	0.519	neutral	None	None	None	None	I
V/F	0.1676	likely_benign	0.1981	benign	-0.957	Destabilizing	0.994	D	0.831	deleterious	N	0.502087984	None	None	I
V/G	0.3068	likely_benign	0.3401	ambiguous	-1.262	Destabilizing	0.967	D	0.795	deleterious	N	0.481115247	None	None	I
V/H	0.5913	likely_pathogenic	0.6579	pathogenic	-0.641	Destabilizing	0.997	D	0.822	deleterious	None	None	None	None	I
V/I	0.0663	likely_benign	0.0684	benign	-0.559	Destabilizing	0.873	D	0.579	neutral	N	0.493929861	None	None	I
V/K	0.3327	likely_benign	0.419	ambiguous	-0.729	Destabilizing	0.95	D	0.792	deleterious	None	None	None	None	I
V/L	0.1765	likely_benign	0.21	benign	-0.559	Destabilizing	0.773	D	0.629	neutral	N	0.442231604	None	None	I
V/M	0.1264	likely_benign	0.1532	benign	-0.445	Destabilizing	0.996	D	0.801	deleterious	None	None	None	None	I
V/N	0.335	likely_benign	0.4107	ambiguous	-0.446	Destabilizing	0.975	D	0.83	deleterious	None	None	None	None	I
V/P	0.3565	ambiguous	0.3965	ambiguous	-0.682	Destabilizing	0.987	D	0.835	deleterious	None	None	None	None	I
V/Q	0.3437	ambiguous	0.4129	ambiguous	-0.69	Destabilizing	0.95	D	0.831	deleterious	None	None	None	None	I
V/R	0.3037	likely_benign	0.3732	ambiguous	-0.15	Destabilizing	0.975	D	0.833	deleterious	None	None	None	None	I
V/S	0.2347	likely_benign	0.2787	benign	-0.971	Destabilizing	0.975	D	0.786	deleterious	None	None	None	None	I
V/T	0.1341	likely_benign	0.1511	benign	-0.929	Destabilizing	0.916	D	0.722	prob.delet.	None	None	None	None	I
V/W	0.7567	likely_pathogenic	0.7901	pathogenic	-1.002	Destabilizing	0.999	D	0.783	deleterious	None	None	None	None	I
V/Y	0.5273	ambiguous	0.5751	pathogenic	-0.732	Destabilizing	0.996	D	0.833	deleterious	None	None	None	None	I

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.