TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5784	17575;17576;17577	chr2:178731416;178731415;178731414	chr2:179596143;179596142;179596141
N2AB	5467	16624;16625;16626	chr2:178731416;178731415;178731414	chr2:179596143;179596142;179596141
N2A	4540	13843;13844;13845	chr2:178731416;178731415;178731414	chr2:179596143;179596142;179596141
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: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-41
• Domain position: 55
• Structural Position: 135
• Q(SASA): 0.2715
• 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/M	rs2080478470	None	0.934	D	0.517	0.195	0.502254315933	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
V/M	rs2080478470	None	0.934	D	0.517	0.195	0.502254315933	gnomAD-4.0.0	6.57324E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47042E-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
V/A	0.1883	likely_benign	0.1816	benign	-1.514	Destabilizing	0.051	N	0.119	neutral	D	0.534846269	None	None	N
V/C	0.7514	likely_pathogenic	0.7362	pathogenic	-1.216	Destabilizing	0.998	D	0.566	neutral	None	None	None	None	N
V/D	0.3778	ambiguous	0.3616	ambiguous	-1.407	Destabilizing	0.974	D	0.656	neutral	None	None	None	None	N
V/E	0.241	likely_benign	0.233	benign	-1.411	Destabilizing	0.801	D	0.615	neutral	D	0.533806119	None	None	N
V/F	0.1553	likely_benign	0.1635	benign	-1.324	Destabilizing	0.949	D	0.595	neutral	None	None	None	None	N
V/G	0.3213	likely_benign	0.3233	benign	-1.818	Destabilizing	0.801	D	0.641	neutral	N	0.49836818	None	None	N
V/H	0.4873	ambiguous	0.4657	ambiguous	-1.358	Destabilizing	0.037	N	0.491	neutral	None	None	None	None	N
V/I	0.0672	likely_benign	0.068	benign	-0.779	Destabilizing	0.016	N	0.149	neutral	None	None	None	None	N
V/K	0.3017	likely_benign	0.2818	benign	-1.096	Destabilizing	0.842	D	0.617	neutral	None	None	None	None	N
V/L	0.19	likely_benign	0.1881	benign	-0.779	Destabilizing	0.454	N	0.397	neutral	N	0.49388508	None	None	N
V/M	0.1042	likely_benign	0.1055	benign	-0.662	Destabilizing	0.934	D	0.517	neutral	D	0.52824837	None	None	N
V/N	0.2684	likely_benign	0.2626	benign	-0.941	Destabilizing	0.949	D	0.653	neutral	None	None	None	None	N
V/P	0.9734	likely_pathogenic	0.972	pathogenic	-0.99	Destabilizing	0.991	D	0.633	neutral	None	None	None	None	N
V/Q	0.2756	likely_benign	0.2615	benign	-1.149	Destabilizing	0.974	D	0.643	neutral	None	None	None	None	N
V/R	0.2709	likely_benign	0.2535	benign	-0.614	Destabilizing	0.974	D	0.667	neutral	None	None	None	None	N
V/S	0.224	likely_benign	0.2177	benign	-1.493	Destabilizing	0.728	D	0.594	neutral	None	None	None	None	N
V/T	0.1331	likely_benign	0.1282	benign	-1.386	Destabilizing	0.029	N	0.117	neutral	None	None	None	None	N
V/W	0.7491	likely_pathogenic	0.7587	pathogenic	-1.477	Destabilizing	0.998	D	0.681	prob.neutral	None	None	None	None	N
V/Y	0.4877	ambiguous	0.4711	ambiguous	-1.161	Destabilizing	0.949	D	0.595	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.