TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26369	79330;79331;79332	chr2:178567027;178567026;178567025	chr2:179431754;179431753;179431752
N2AB	24728	74407;74408;74409	chr2:178567027;178567026;178567025	chr2:179431754;179431753;179431752
N2A	23801	71626;71627;71628	chr2:178567027;178567026;178567025	chr2:179431754;179431753;179431752
N2B	17304	52135;52136;52137	chr2:178567027;178567026;178567025	chr2:179431754;179431753;179431752
Novex-1	17429	52510;52511;52512	chr2:178567027;178567026;178567025	chr2:179431754;179431753;179431752
Novex-2	17496	52711;52712;52713	chr2:178567027;178567026;178567025	chr2:179431754;179431753;179431752
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: Fn3-79
• Domain position: 84
• Structural Position: 117
• Q(SASA): 0.3949
• 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	0.062	N	0.571	0.217	0.57186346447	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
V/I	rs778729064	-0.685	None	N	0.257	0.056	0.195762928549	gnomAD-3.1.2	1.97E-05	None	None	None	None	I	None	0	1.31079E-04	0	0	0	None	0	0	0	0	4.78011E-04
V/I	rs778729064	-0.685	None	N	0.257	0.056	0.195762928549	gnomAD-4.0.0	8.96861E-06	None	None	None	None	I	None	0	3.38903E-05	None	0	0	None	0	0	0	0	1.42207E-04

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	0.1119	likely_benign	0.1306	benign	-1.174	Destabilizing	None	N	0.247	neutral	N	0.492409708	None	None	I
V/C	0.6001	likely_pathogenic	0.6282	pathogenic	-0.926	Destabilizing	0.824	D	0.566	neutral	None	None	None	None	I
V/D	0.4497	ambiguous	0.4936	ambiguous	-0.758	Destabilizing	None	N	0.513	neutral	N	0.465012455	None	None	I
V/E	0.3365	likely_benign	0.3673	ambiguous	-0.828	Destabilizing	0.002	N	0.478	neutral	None	None	None	None	I
V/F	0.1653	likely_benign	0.1759	benign	-1.096	Destabilizing	0.317	N	0.585	neutral	N	0.47967367	None	None	I
V/G	0.224	likely_benign	0.2628	benign	-1.398	Destabilizing	0.062	N	0.571	neutral	N	0.480456911	None	None	I
V/H	0.5709	likely_pathogenic	0.5875	pathogenic	-0.769	Destabilizing	0.935	D	0.617	neutral	None	None	None	None	I
V/I	0.0661	likely_benign	0.0634	benign	-0.699	Destabilizing	None	N	0.257	neutral	N	0.44733078	None	None	I
V/K	0.3584	ambiguous	0.3819	ambiguous	-0.859	Destabilizing	0.149	N	0.614	neutral	None	None	None	None	I
V/L	0.1747	likely_benign	0.1585	benign	-0.699	Destabilizing	0.009	N	0.465	neutral	N	0.472399795	None	None	I
V/M	0.1282	likely_benign	0.1295	benign	-0.561	Destabilizing	0.38	N	0.597	neutral	None	None	None	None	I
V/N	0.2815	likely_benign	0.295	benign	-0.601	Destabilizing	0.38	N	0.609	neutral	None	None	None	None	I
V/P	0.3204	likely_benign	0.3436	ambiguous	-0.821	Destabilizing	0.38	N	0.613	neutral	None	None	None	None	I
V/Q	0.3268	likely_benign	0.3412	ambiguous	-0.873	Destabilizing	0.38	N	0.621	neutral	None	None	None	None	I
V/R	0.3052	likely_benign	0.3311	benign	-0.245	Destabilizing	0.38	N	0.623	neutral	None	None	None	None	I
V/S	0.1647	likely_benign	0.1983	benign	-1.102	Destabilizing	0.081	N	0.568	neutral	None	None	None	None	I
V/T	0.1124	likely_benign	0.1132	benign	-1.067	Destabilizing	0.001	N	0.221	neutral	None	None	None	None	I
V/W	0.7745	likely_pathogenic	0.7831	pathogenic	-1.127	Destabilizing	0.935	D	0.661	neutral	None	None	None	None	I
V/Y	0.5237	ambiguous	0.5275	ambiguous	-0.865	Destabilizing	0.555	D	0.581	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.