TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	960	3103;3104;3105	chr2:178783028;178783027;178783026	chr2:179647755;179647754;179647753
N2AB	960	3103;3104;3105	chr2:178783028;178783027;178783026	chr2:179647755;179647754;179647753
N2A	960	3103;3104;3105	chr2:178783028;178783027;178783026	chr2:179647755;179647754;179647753
N2B	914	2965;2966;2967	chr2:178783028;178783027;178783026	chr2:179647755;179647754;179647753
Novex-1	914	2965;2966;2967	chr2:178783028;178783027;178783026	chr2:179647755;179647754;179647753
Novex-2	914	2965;2966;2967	chr2:178783028;178783027;178783026	chr2:179647755;179647754;179647753
Novex-3	960	3103;3104;3105	chr2:178783028;178783027;178783026	chr2:179647755;179647754;179647753

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-3
• Domain position: 18
• Structural Position: 28
• Q(SASA): 0.1878
• 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	0.046	D	0.243	0.256	0.493628743246	gnomAD-4.0.0	1.36821E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79868E-06	0	0
V/L	None	None	0.046	N	0.242	0.357	0.411001663086	gnomAD-4.0.0	6.84104E-07	None	None	None	None	N	None	2.98704E-05	0	None	0	0	None	0	0	0	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	0.7364	likely_pathogenic	0.7337	pathogenic	-1.572	Destabilizing	0.939	D	0.533	neutral	D	0.523340756	None	None	N
V/C	0.9716	likely_pathogenic	0.9723	pathogenic	-1.434	Destabilizing	0.999	D	0.7	prob.neutral	None	None	None	None	N
V/D	0.9963	likely_pathogenic	0.9969	pathogenic	-0.986	Destabilizing	0.997	D	0.792	deleterious	D	0.791481458	None	None	N
V/E	0.9815	likely_pathogenic	0.9846	pathogenic	-0.933	Destabilizing	0.998	D	0.757	deleterious	None	None	None	None	N
V/F	0.8797	likely_pathogenic	0.8989	pathogenic	-1.119	Destabilizing	0.982	D	0.765	deleterious	D	0.630505523	None	None	N
V/G	0.9461	likely_pathogenic	0.9498	pathogenic	-1.952	Destabilizing	0.997	D	0.798	deleterious	D	0.663453342	None	None	N
V/H	0.9966	likely_pathogenic	0.9972	pathogenic	-1.426	Destabilizing	0.999	D	0.761	deleterious	None	None	None	None	N
V/I	0.1484	likely_benign	0.1536	benign	-0.611	Destabilizing	0.046	N	0.243	neutral	D	0.529530056	None	None	N
V/K	0.9816	likely_pathogenic	0.985	pathogenic	-1.289	Destabilizing	0.993	D	0.761	deleterious	None	None	None	None	N
V/L	0.8142	likely_pathogenic	0.8358	pathogenic	-0.611	Destabilizing	0.046	N	0.242	neutral	N	0.518464429	None	None	N
V/M	0.7297	likely_pathogenic	0.7604	pathogenic	-0.66	Destabilizing	0.986	D	0.648	neutral	None	None	None	None	N
V/N	0.9899	likely_pathogenic	0.9919	pathogenic	-1.199	Destabilizing	0.998	D	0.808	deleterious	None	None	None	None	N
V/P	0.9981	likely_pathogenic	0.9984	pathogenic	-0.896	Destabilizing	0.998	D	0.739	prob.delet.	None	None	None	None	N
V/Q	0.9778	likely_pathogenic	0.9819	pathogenic	-1.251	Destabilizing	0.998	D	0.757	deleterious	None	None	None	None	N
V/R	0.9736	likely_pathogenic	0.9784	pathogenic	-0.902	Destabilizing	0.998	D	0.808	deleterious	None	None	None	None	N
V/S	0.9502	likely_pathogenic	0.9524	pathogenic	-1.873	Destabilizing	0.993	D	0.757	deleterious	None	None	None	None	N
V/T	0.8177	likely_pathogenic	0.8215	pathogenic	-1.677	Destabilizing	0.953	D	0.613	neutral	None	None	None	None	N
V/W	0.9988	likely_pathogenic	0.999	pathogenic	-1.286	Destabilizing	0.999	D	0.737	prob.delet.	None	None	None	None	N
V/Y	0.9919	likely_pathogenic	0.9934	pathogenic	-0.986	Destabilizing	0.998	D	0.737	prob.delet.	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.