TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2879	8860;8861;8862	chr2:178770066;178770065;178770064	chr2:179634793;179634792;179634791
N2AB	2879	8860;8861;8862	chr2:178770066;178770065;178770064	chr2:179634793;179634792;179634791
N2A	2879	8860;8861;8862	chr2:178770066;178770065;178770064	chr2:179634793;179634792;179634791
N2B	2833	8722;8723;8724	chr2:178770066;178770065;178770064	chr2:179634793;179634792;179634791
Novex-1	2833	8722;8723;8724	chr2:178770066;178770065;178770064	chr2:179634793;179634792;179634791
Novex-2	2833	8722;8723;8724	chr2:178770066;178770065;178770064	chr2:179634793;179634792;179634791
Novex-3	2879	8860;8861;8862	chr2:178770066;178770065;178770064	chr2:179634793;179634792;179634791

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-18
• Domain position: 85
• Structural Position: 177
• Q(SASA): 0.1281
• 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	None	None	0.999	D	0.529	0.676	0.692093607395	gnomAD-4.0.0	1.59047E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85647E-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	0.8079	likely_pathogenic	0.8187	pathogenic	-1.772	Destabilizing	0.999	D	0.529	neutral	D	0.698542044	None	None	N
V/C	0.9646	likely_pathogenic	0.9667	pathogenic	-1.278	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	N
V/D	0.997	likely_pathogenic	0.9965	pathogenic	-1.978	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
V/E	0.9883	likely_pathogenic	0.9876	pathogenic	-1.935	Destabilizing	1.0	D	0.696	prob.neutral	D	0.700784897	None	None	N
V/F	0.9201	likely_pathogenic	0.9105	pathogenic	-1.292	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
V/G	0.9409	likely_pathogenic	0.9402	pathogenic	-2.134	Highly Destabilizing	1.0	D	0.723	prob.delet.	D	0.700784897	None	None	N
V/H	0.9966	likely_pathogenic	0.9964	pathogenic	-1.711	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
V/I	0.1188	likely_benign	0.1202	benign	-0.846	Destabilizing	0.998	D	0.473	neutral	None	None	None	None	N
V/K	0.9898	likely_pathogenic	0.9886	pathogenic	-1.457	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	N
V/L	0.7361	likely_pathogenic	0.752	pathogenic	-0.846	Destabilizing	0.997	D	0.507	neutral	D	0.635606197	None	None	N
V/M	0.7491	likely_pathogenic	0.7653	pathogenic	-0.721	Destabilizing	1.0	D	0.72	prob.delet.	D	0.70015623	None	None	N
V/N	0.9896	likely_pathogenic	0.9892	pathogenic	-1.355	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
V/P	0.9819	likely_pathogenic	0.9793	pathogenic	-1.123	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
V/Q	0.9855	likely_pathogenic	0.986	pathogenic	-1.494	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
V/R	0.9811	likely_pathogenic	0.9792	pathogenic	-0.986	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
V/S	0.9336	likely_pathogenic	0.9403	pathogenic	-1.885	Destabilizing	1.0	D	0.696	prob.neutral	None	None	None	None	N
V/T	0.7488	likely_pathogenic	0.7687	pathogenic	-1.735	Destabilizing	0.999	D	0.615	neutral	None	None	None	None	N
V/W	0.9982	likely_pathogenic	0.998	pathogenic	-1.559	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
V/Y	0.9936	likely_pathogenic	0.9935	pathogenic	-1.258	Destabilizing	1.0	D	0.729	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.