TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6974	21145;21146;21147	chr2:178724455;178724454;178724453	chr2:179589182;179589181;179589180
N2AB	6657	20194;20195;20196	chr2:178724455;178724454;178724453	chr2:179589182;179589181;179589180
N2A	5730	17413;17414;17415	chr2:178724455;178724454;178724453	chr2:179589182;179589181;179589180
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-54
• Domain position: 27
• Structural Position: 41
• Q(SASA): 0.7215
• 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
T/P	None	None	0.999	D	0.672	0.444	0.649470034893	gnomAD-4.0.0	3.60097E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.9375E-06	0	0
T/S	rs774828625	-0.038	0.905	N	0.383	0.166	0.329282125956	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	5.58E-05	None	0	None	0	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
T/A	0.2479	likely_benign	0.1691	benign	-0.165	Destabilizing	0.981	D	0.512	neutral	N	0.482380008	None	None	I
T/C	0.8184	likely_pathogenic	0.7459	pathogenic	-0.289	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	I
T/D	0.5592	ambiguous	0.4932	ambiguous	0.15	Stabilizing	0.999	D	0.615	neutral	None	None	None	None	I
T/E	0.5915	likely_pathogenic	0.467	ambiguous	0.069	Stabilizing	0.999	D	0.617	neutral	None	None	None	None	I
T/F	0.4117	ambiguous	0.2843	benign	-0.731	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	I
T/G	0.5132	ambiguous	0.4483	ambiguous	-0.261	Destabilizing	0.997	D	0.639	neutral	None	None	None	None	I
T/H	0.4492	ambiguous	0.3518	ambiguous	-0.408	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	I
T/I	0.4731	ambiguous	0.3106	benign	-0.033	Destabilizing	0.999	D	0.685	prob.neutral	N	0.486999181	None	None	I
T/K	0.4602	ambiguous	0.3214	benign	-0.26	Destabilizing	0.999	D	0.622	neutral	None	None	None	None	I
T/L	0.2479	likely_benign	0.1645	benign	-0.033	Destabilizing	0.998	D	0.61	neutral	None	None	None	None	I
T/M	0.1733	likely_benign	0.1192	benign	-0.091	Destabilizing	1.0	D	0.698	prob.neutral	None	None	None	None	I
T/N	0.1943	likely_benign	0.1366	benign	-0.03	Destabilizing	0.999	D	0.676	prob.neutral	N	0.456790917	None	None	I
T/P	0.5557	ambiguous	0.5136	ambiguous	-0.05	Destabilizing	0.999	D	0.672	neutral	D	0.53377162	None	None	I
T/Q	0.4761	ambiguous	0.3466	ambiguous	-0.235	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	I
T/R	0.4456	ambiguous	0.3077	benign	0.043	Stabilizing	1.0	D	0.673	neutral	None	None	None	None	I
T/S	0.1364	likely_benign	0.1131	benign	-0.219	Destabilizing	0.905	D	0.383	neutral	N	0.467391913	None	None	I
T/V	0.4127	ambiguous	0.2619	benign	-0.05	Destabilizing	0.998	D	0.623	neutral	None	None	None	None	I
T/W	0.7734	likely_pathogenic	0.695	pathogenic	-0.8	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	I
T/Y	0.4226	ambiguous	0.312	benign	-0.483	Destabilizing	1.0	D	0.761	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.