TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9216	27871;27872;27873	chr2:178712184;178712183;178712182	chr2:179576911;179576910;179576909
N2AB	8899	26920;26921;26922	chr2:178712184;178712183;178712182	chr2:179576911;179576910;179576909
N2A	7972	24139;24140;24141	chr2:178712184;178712183;178712182	chr2:179576911;179576910;179576909
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-78
• Domain position: 12
• Structural Position: 16
• Q(SASA): 0.7031
• 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/L	rs2076754022	None	0.981	N	0.472	0.399	0.593798965771	gnomAD-4.0.0	1.59154E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85889E-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	0.208	likely_benign	0.1895	benign	-1.676	Destabilizing	0.998	D	0.488	neutral	N	0.499045758	None	None	I
V/C	0.8514	likely_pathogenic	0.8519	pathogenic	-1.341	Destabilizing	1.0	D	0.623	neutral	None	None	None	None	I
V/D	0.7494	likely_pathogenic	0.685	pathogenic	-1.583	Destabilizing	1.0	D	0.684	prob.neutral	None	None	None	None	I
V/E	0.6779	likely_pathogenic	0.6229	pathogenic	-1.55	Destabilizing	1.0	D	0.618	neutral	D	0.528927002	None	None	I
V/F	0.3862	ambiguous	0.3286	benign	-1.253	Destabilizing	1.0	D	0.619	neutral	None	None	None	None	I
V/G	0.2935	likely_benign	0.2637	benign	-2.027	Highly Destabilizing	1.0	D	0.663	neutral	N	0.510569258	None	None	I
V/H	0.894	likely_pathogenic	0.8622	pathogenic	-1.522	Destabilizing	1.0	D	0.678	prob.neutral	None	None	None	None	I
V/I	0.1196	likely_benign	0.1173	benign	-0.792	Destabilizing	0.813	D	0.262	neutral	None	None	None	None	I
V/K	0.7522	likely_pathogenic	0.6828	pathogenic	-1.315	Destabilizing	1.0	D	0.619	neutral	None	None	None	None	I
V/L	0.4413	ambiguous	0.3722	ambiguous	-0.792	Destabilizing	0.981	D	0.472	neutral	N	0.492639132	None	None	I
V/M	0.3155	likely_benign	0.292	benign	-0.743	Destabilizing	0.999	D	0.688	prob.neutral	D	0.528420023	None	None	I
V/N	0.6583	likely_pathogenic	0.5934	pathogenic	-1.201	Destabilizing	1.0	D	0.68	prob.neutral	None	None	None	None	I
V/P	0.9505	likely_pathogenic	0.9374	pathogenic	-1.053	Destabilizing	1.0	D	0.655	neutral	None	None	None	None	I
V/Q	0.7209	likely_pathogenic	0.6591	pathogenic	-1.35	Destabilizing	1.0	D	0.654	neutral	None	None	None	None	I
V/R	0.703	likely_pathogenic	0.6254	pathogenic	-0.849	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	I
V/S	0.4094	ambiguous	0.3698	ambiguous	-1.789	Destabilizing	1.0	D	0.642	neutral	None	None	None	None	I
V/T	0.2774	likely_benign	0.2591	benign	-1.641	Destabilizing	0.998	D	0.644	neutral	None	None	None	None	I
V/W	0.9625	likely_pathogenic	0.95	pathogenic	-1.447	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	I
V/Y	0.8281	likely_pathogenic	0.776	pathogenic	-1.144	Destabilizing	1.0	D	0.656	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.