TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25072	75439;75440;75441	chr2:178570918;178570917;178570916	chr2:179435645;179435644;179435643
N2AB	23431	70516;70517;70518	chr2:178570918;178570917;178570916	chr2:179435645;179435644;179435643
N2A	22504	67735;67736;67737	chr2:178570918;178570917;178570916	chr2:179435645;179435644;179435643
N2B	16007	48244;48245;48246	chr2:178570918;178570917;178570916	chr2:179435645;179435644;179435643
Novex-1	16132	48619;48620;48621	chr2:178570918;178570917;178570916	chr2:179435645;179435644;179435643
Novex-2	16199	48820;48821;48822	chr2:178570918;178570917;178570916	chr2:179435645;179435644;179435643
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: Fn3-70
• Domain position: 67
• Structural Position: 98
• Q(SASA): 0.433
• 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/A	rs1707961422	None	None	N	0.082	0.126	0.238096912614	gnomAD-4.0.0	2.73714E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79916E-06	2.31868E-05	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	0.1336	likely_benign	0.1136	benign	-1.353	Destabilizing	None	N	0.082	neutral	N	0.467455336	None	None	N
V/C	0.7066	likely_pathogenic	0.6716	pathogenic	-0.719	Destabilizing	0.824	D	0.357	neutral	None	None	None	None	N
V/D	0.4226	ambiguous	0.359	ambiguous	-1.259	Destabilizing	0.484	N	0.374	neutral	N	0.490697555	None	None	N
V/E	0.3161	likely_benign	0.2752	benign	-1.28	Destabilizing	0.38	N	0.353	neutral	None	None	None	None	N
V/F	0.2145	likely_benign	0.1918	benign	-1.138	Destabilizing	0.188	N	0.375	neutral	N	0.482040786	None	None	N
V/G	0.235	likely_benign	0.1969	benign	-1.639	Destabilizing	0.062	N	0.372	neutral	N	0.470545864	None	None	N
V/H	0.529	ambiguous	0.4898	ambiguous	-1.143	Destabilizing	0.935	D	0.373	neutral	None	None	None	None	N
V/I	0.077	likely_benign	0.0773	benign	-0.676	Destabilizing	None	N	0.087	neutral	N	0.442290319	None	None	N
V/K	0.3336	likely_benign	0.3034	benign	-1.113	Destabilizing	0.149	N	0.354	neutral	None	None	None	None	N
V/L	0.1703	likely_benign	0.152	benign	-0.676	Destabilizing	None	N	0.078	neutral	N	0.448253499	None	None	N
V/M	0.1277	likely_benign	0.1187	benign	-0.449	Destabilizing	0.235	N	0.349	neutral	None	None	None	None	N
V/N	0.2471	likely_benign	0.2045	benign	-0.832	Destabilizing	0.555	D	0.395	neutral	None	None	None	None	N
V/P	0.6424	likely_pathogenic	0.5671	pathogenic	-0.867	Destabilizing	0.555	D	0.383	neutral	None	None	None	None	N
V/Q	0.2938	likely_benign	0.267	benign	-1.033	Destabilizing	0.555	D	0.37	neutral	None	None	None	None	N
V/R	0.2922	likely_benign	0.2735	benign	-0.533	Destabilizing	0.38	N	0.386	neutral	None	None	None	None	N
V/S	0.1655	likely_benign	0.1416	benign	-1.276	Destabilizing	0.081	N	0.333	neutral	None	None	None	None	N
V/T	0.0989	likely_benign	0.0947	benign	-1.192	Destabilizing	0.001	N	0.072	neutral	None	None	None	None	N
V/W	0.8159	likely_pathogenic	0.7762	pathogenic	-1.313	Destabilizing	0.935	D	0.42	neutral	None	None	None	None	N
V/Y	0.589	likely_pathogenic	0.5278	ambiguous	-1.029	Destabilizing	0.555	D	0.367	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.