TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18216	54871;54872;54873	chr2:178604041;178604040;178604039	chr2:179468768;179468767;179468766
N2AB	16575	49948;49949;49950	chr2:178604041;178604040;178604039	chr2:179468768;179468767;179468766
N2A	15648	47167;47168;47169	chr2:178604041;178604040;178604039	chr2:179468768;179468767;179468766
N2B	9151	27676;27677;27678	chr2:178604041;178604040;178604039	chr2:179468768;179468767;179468766
Novex-1	9276	28051;28052;28053	chr2:178604041;178604040;178604039	chr2:179468768;179468767;179468766
Novex-2	9343	28252;28253;28254	chr2:178604041;178604040;178604039	chr2:179468768;179468767;179468766
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: Fn3-20
• Domain position: 51
• Structural Position: 68
• Q(SASA): 0.2307
• 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/I	rs2054164910	None	0.997	N	0.459	0.253	0.630072707612	gnomAD-3.1.2	1.32E-05	None	None	None	None	I	None	0	1.31268E-04	0	0	0	None	0	0	0	0	0
V/I	rs2054164910	None	0.997	N	0.459	0.253	0.630072707612	gnomAD-4.0.0	5.13006E-06	None	None	None	None	I	None	0	5.08802E-05	None	0	0	None	0	0	2.39621E-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	0.5207	ambiguous	0.3947	ambiguous	-1.215	Destabilizing	0.999	D	0.539	neutral	N	0.501357265	None	None	I
V/C	0.8547	likely_pathogenic	0.8487	pathogenic	-0.976	Destabilizing	1.0	D	0.764	deleterious	None	None	None	None	I
V/D	0.9817	likely_pathogenic	0.9685	pathogenic	-0.661	Destabilizing	1.0	D	0.82	deleterious	D	0.525708003	None	None	I
V/E	0.9556	likely_pathogenic	0.9071	pathogenic	-0.516	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	I
V/F	0.8117	likely_pathogenic	0.6639	pathogenic	-0.583	Destabilizing	1.0	D	0.769	deleterious	N	0.473962451	None	None	I
V/G	0.7621	likely_pathogenic	0.6603	pathogenic	-1.66	Destabilizing	1.0	D	0.786	deleterious	N	0.488107141	None	None	I
V/H	0.9874	likely_pathogenic	0.9756	pathogenic	-1.185	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	I
V/I	0.1472	likely_benign	0.1189	benign	-0.042	Destabilizing	0.997	D	0.459	neutral	N	0.511976904	None	None	I
V/K	0.9825	likely_pathogenic	0.9706	pathogenic	-0.898	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	I
V/L	0.7328	likely_pathogenic	0.5447	ambiguous	-0.042	Destabilizing	0.997	D	0.513	neutral	N	0.502471986	None	None	I
V/M	0.7214	likely_pathogenic	0.5471	ambiguous	-0.246	Destabilizing	1.0	D	0.674	neutral	None	None	None	None	I
V/N	0.9357	likely_pathogenic	0.9059	pathogenic	-1.052	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	I
V/P	0.9509	likely_pathogenic	0.9506	pathogenic	-0.399	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	I
V/Q	0.9563	likely_pathogenic	0.9186	pathogenic	-0.921	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	I
V/R	0.9686	likely_pathogenic	0.9489	pathogenic	-0.793	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	I
V/S	0.766	likely_pathogenic	0.683	pathogenic	-1.741	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	I
V/T	0.6653	likely_pathogenic	0.5877	pathogenic	-1.442	Destabilizing	0.999	D	0.536	neutral	None	None	None	None	I
V/W	0.9957	likely_pathogenic	0.9897	pathogenic	-0.897	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	I
V/Y	0.9747	likely_pathogenic	0.9505	pathogenic	-0.492	Destabilizing	1.0	D	0.777	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.