TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	977	3154;3155;3156	chr2:178782977;178782976;178782975	chr2:179647704;179647703;179647702
N2AB	977	3154;3155;3156	chr2:178782977;178782976;178782975	chr2:179647704;179647703;179647702
N2A	977	3154;3155;3156	chr2:178782977;178782976;178782975	chr2:179647704;179647703;179647702
N2B	931	3016;3017;3018	chr2:178782977;178782976;178782975	chr2:179647704;179647703;179647702
Novex-1	931	3016;3017;3018	chr2:178782977;178782976;178782975	chr2:179647704;179647703;179647702
Novex-2	931	3016;3017;3018	chr2:178782977;178782976;178782975	chr2:179647704;179647703;179647702
Novex-3	977	3154;3155;3156	chr2:178782977;178782976;178782975	chr2:179647704;179647703;179647702

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-3
• Domain position: 35
• Structural Position: 49
• Q(SASA): 0.2479
• 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
Y/C	rs1305432524	-1.384	0.999	D	0.714	0.625	0.845155949937	gnomAD-2.1.1	7.97E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.77E-05	0
Y/C	rs1305432524	-1.384	0.999	D	0.714	0.625	0.845155949937	gnomAD-4.0.0	3.18107E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71311E-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
Y/A	0.9541	likely_pathogenic	0.9686	pathogenic	-2.449	Highly Destabilizing	0.959	D	0.644	neutral	None	None	None	None	N
Y/C	0.6987	likely_pathogenic	0.7559	pathogenic	-1.118	Destabilizing	0.999	D	0.714	prob.delet.	D	0.704306849	None	None	N
Y/D	0.9139	likely_pathogenic	0.943	pathogenic	-1.123	Destabilizing	0.995	D	0.725	prob.delet.	D	0.61435215	None	None	N
Y/E	0.955	likely_pathogenic	0.9696	pathogenic	-1.061	Destabilizing	0.996	D	0.715	prob.delet.	None	None	None	None	N
Y/F	0.1042	likely_benign	0.1016	benign	-1.253	Destabilizing	0.011	N	0.225	neutral	N	0.490595103	None	None	N
Y/G	0.9333	likely_pathogenic	0.9536	pathogenic	-2.745	Highly Destabilizing	0.988	D	0.699	prob.neutral	None	None	None	None	N
Y/H	0.4876	ambiguous	0.5272	ambiguous	-1.093	Destabilizing	0.995	D	0.603	neutral	D	0.566606762	None	None	N
Y/I	0.851	likely_pathogenic	0.883	pathogenic	-1.556	Destabilizing	0.851	D	0.632	neutral	None	None	None	None	N
Y/K	0.9175	likely_pathogenic	0.9339	pathogenic	-1.029	Destabilizing	0.996	D	0.719	prob.delet.	None	None	None	None	N
Y/L	0.7892	likely_pathogenic	0.8194	pathogenic	-1.556	Destabilizing	0.702	D	0.587	neutral	None	None	None	None	N
Y/M	0.8577	likely_pathogenic	0.883	pathogenic	-1.189	Destabilizing	0.988	D	0.705	prob.neutral	None	None	None	None	N
Y/N	0.6562	likely_pathogenic	0.7119	pathogenic	-1.199	Destabilizing	0.995	D	0.724	prob.delet.	D	0.603333791	None	None	N
Y/P	0.9993	likely_pathogenic	0.9996	pathogenic	-1.849	Destabilizing	0.996	D	0.727	prob.delet.	None	None	None	None	N
Y/Q	0.885	likely_pathogenic	0.9139	pathogenic	-1.277	Destabilizing	0.996	D	0.701	prob.neutral	None	None	None	None	N
Y/R	0.8506	likely_pathogenic	0.8825	pathogenic	-0.438	Destabilizing	0.996	D	0.723	prob.delet.	None	None	None	None	N
Y/S	0.7538	likely_pathogenic	0.8117	pathogenic	-1.819	Destabilizing	0.984	D	0.696	prob.neutral	D	0.525221966	None	None	N
Y/T	0.8966	likely_pathogenic	0.9229	pathogenic	-1.662	Destabilizing	0.988	D	0.694	prob.neutral	None	None	None	None	N
Y/V	0.815	likely_pathogenic	0.8565	pathogenic	-1.849	Destabilizing	0.919	D	0.569	neutral	None	None	None	None	N
Y/W	0.6537	likely_pathogenic	0.6697	pathogenic	-0.786	Destabilizing	0.996	D	0.605	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.