TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5315	16168;16169;16170	chr2:178733350;178733349;178733348	chr2:179598077;179598076;179598075
N2AB	4998	15217;15218;15219	chr2:178733350;178733349;178733348	chr2:179598077;179598076;179598075
N2A	4071	12436;12437;12438	chr2:178733350;178733349;178733348	chr2:179598077;179598076;179598075
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: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-36
• Domain position: 55
• Structural Position: 135
• Q(SASA): 0.2856
• 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/I	None	None	None	N	0.151	0.089	0.336647302497	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.2301	likely_benign	0.2789	benign	-1.607	Destabilizing	0.052	N	0.411	neutral	D	0.530776786	None	None	N
V/C	0.7673	likely_pathogenic	0.8103	pathogenic	-1.098	Destabilizing	0.935	D	0.559	neutral	None	None	None	None	N
V/D	0.4961	ambiguous	0.5866	pathogenic	-1.685	Destabilizing	0.484	N	0.641	neutral	D	0.530238119	None	None	N
V/E	0.3393	likely_benign	0.3858	ambiguous	-1.674	Destabilizing	0.555	D	0.589	neutral	None	None	None	None	N
V/F	0.1958	likely_benign	0.221	benign	-1.274	Destabilizing	0.317	N	0.583	neutral	D	0.555795603	None	None	N
V/G	0.3909	ambiguous	0.4729	ambiguous	-1.936	Destabilizing	0.484	N	0.615	neutral	N	0.508048647	None	None	N
V/H	0.5502	ambiguous	0.6213	pathogenic	-1.509	Destabilizing	0.935	D	0.658	neutral	None	None	None	None	N
V/I	0.0652	likely_benign	0.0647	benign	-0.788	Destabilizing	None	N	0.151	neutral	N	0.493921296	None	None	N
V/K	0.3119	likely_benign	0.3487	ambiguous	-1.23	Destabilizing	0.555	D	0.594	neutral	None	None	None	None	N
V/L	0.2111	likely_benign	0.2377	benign	-0.788	Destabilizing	0.009	N	0.365	neutral	N	0.505537016	None	None	N
V/M	0.1292	likely_benign	0.1419	benign	-0.615	Destabilizing	0.38	N	0.482	neutral	None	None	None	None	N
V/N	0.3366	likely_benign	0.3866	ambiguous	-1.062	Destabilizing	0.555	D	0.659	neutral	None	None	None	None	N
V/P	0.9655	likely_pathogenic	0.9807	pathogenic	-1.028	Destabilizing	0.791	D	0.635	neutral	None	None	None	None	N
V/Q	0.3265	likely_benign	0.3617	ambiguous	-1.249	Destabilizing	0.791	D	0.65	neutral	None	None	None	None	N
V/R	0.2813	likely_benign	0.3185	benign	-0.738	Destabilizing	0.555	D	0.682	prob.neutral	None	None	None	None	N
V/S	0.2842	likely_benign	0.3431	ambiguous	-1.581	Destabilizing	0.081	N	0.591	neutral	None	None	None	None	N
V/T	0.1663	likely_benign	0.1983	benign	-1.465	Destabilizing	0.001	N	0.137	neutral	None	None	None	None	N
V/W	0.8247	likely_pathogenic	0.8723	pathogenic	-1.492	Destabilizing	0.935	D	0.699	prob.neutral	None	None	None	None	N
V/Y	0.5541	ambiguous	0.6098	pathogenic	-1.189	Destabilizing	0.555	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.