TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18915	56968;56969;56970	chr2:178598967;178598966;178598965	chr2:179463694;179463693;179463692
N2AB	17274	52045;52046;52047	chr2:178598967;178598966;178598965	chr2:179463694;179463693;179463692
N2A	16347	49264;49265;49266	chr2:178598967;178598966;178598965	chr2:179463694;179463693;179463692
N2B	9850	29773;29774;29775	chr2:178598967;178598966;178598965	chr2:179463694;179463693;179463692
Novex-1	9975	30148;30149;30150	chr2:178598967;178598966;178598965	chr2:179463694;179463693;179463692
Novex-2	10042	30349;30350;30351	chr2:178598967;178598966;178598965	chr2:179463694;179463693;179463692
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-25
• Domain position: 32
• Structural Position: 34
• Q(SASA): 0.6871
• 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
P/L	rs2052547885	None	0.999	N	0.67	0.446	0.623294314964	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
P/L	rs2052547885	None	0.999	N	0.67	0.446	0.623294314964	gnomAD-4.0.0	6.58007E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.47124E-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
P/A	0.1004	likely_benign	0.1004	benign	-0.414	Destabilizing	0.992	D	0.518	neutral	N	0.51682815	None	None	I
P/C	0.6676	likely_pathogenic	0.6424	pathogenic	-0.537	Destabilizing	1.0	D	0.629	neutral	None	None	None	None	I
P/D	0.5592	ambiguous	0.5692	pathogenic	-0.313	Destabilizing	0.999	D	0.632	neutral	None	None	None	None	I
P/E	0.3088	likely_benign	0.3379	benign	-0.448	Destabilizing	0.999	D	0.633	neutral	None	None	None	None	I
P/F	0.6877	likely_pathogenic	0.6844	pathogenic	-0.83	Destabilizing	1.0	D	0.627	neutral	None	None	None	None	I
P/G	0.5071	ambiguous	0.4773	ambiguous	-0.514	Destabilizing	0.997	D	0.609	neutral	None	None	None	None	I
P/H	0.3167	likely_benign	0.3081	benign	-0.175	Destabilizing	1.0	D	0.618	neutral	N	0.49385804	None	None	I
P/I	0.4306	ambiguous	0.4131	ambiguous	-0.313	Destabilizing	1.0	D	0.67	neutral	None	None	None	None	I
P/K	0.3745	ambiguous	0.3602	ambiguous	-0.243	Destabilizing	0.999	D	0.625	neutral	None	None	None	None	I
P/L	0.1667	likely_benign	0.1688	benign	-0.313	Destabilizing	0.999	D	0.67	neutral	N	0.499391449	None	None	I
P/M	0.3765	ambiguous	0.356	ambiguous	-0.198	Destabilizing	1.0	D	0.623	neutral	None	None	None	None	I
P/N	0.4801	ambiguous	0.4657	ambiguous	0.004	Stabilizing	0.999	D	0.679	prob.neutral	None	None	None	None	I
P/Q	0.2153	likely_benign	0.2105	benign	-0.297	Destabilizing	1.0	D	0.657	neutral	None	None	None	None	I
P/R	0.2661	likely_benign	0.2615	benign	0.274	Stabilizing	0.999	D	0.679	prob.neutral	N	0.477893379	None	None	I
P/S	0.1978	likely_benign	0.1958	benign	-0.329	Destabilizing	0.957	D	0.368	neutral	N	0.473828001	None	None	I
P/T	0.1605	likely_benign	0.1537	benign	-0.369	Destabilizing	0.998	D	0.629	neutral	N	0.518078944	None	None	I
P/V	0.275	likely_benign	0.2606	benign	-0.313	Destabilizing	1.0	D	0.68	prob.neutral	None	None	None	None	I
P/W	0.82	likely_pathogenic	0.8094	pathogenic	-0.89	Destabilizing	1.0	D	0.662	neutral	None	None	None	None	I
P/Y	0.6699	likely_pathogenic	0.642	pathogenic	-0.558	Destabilizing	1.0	D	0.627	neutral	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.