TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14756	44491;44492;44493	chr2:178630256;178630255;178630254	chr2:179494983;179494982;179494981
N2AB	13115	39568;39569;39570	chr2:178630256;178630255;178630254	chr2:179494983;179494982;179494981
N2A	12188	36787;36788;36789	chr2:178630256;178630255;178630254	chr2:179494983;179494982;179494981
N2B	5691	17296;17297;17298	chr2:178630256;178630255;178630254	chr2:179494983;179494982;179494981
Novex-1	5816	17671;17672;17673	chr2:178630256;178630255;178630254	chr2:179494983;179494982;179494981
Novex-2	5883	17872;17873;17874	chr2:178630256;178630255;178630254	chr2:179494983;179494982;179494981
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAC
• RefSeq wild type template codon: GTG
• Domain: Ig-98
• Domain position: 82
• Structural Position: 173
• Q(SASA): 0.3797
• 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
H/N	None	None	0.828	N	0.51	0.214	0.171388866994	gnomAD-4.0.0	1.59299E-06	None	None	None	None	N	None	0	0	None	0	2.77948E-05	None	0	0	0	0	0
H/Y	rs766470098	0.629	0.936	N	0.569	0.216	0.193865811164	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
H/Y	rs766470098	0.629	0.936	N	0.569	0.216	0.193865811164	gnomAD-4.0.0	1.59299E-06	None	None	None	None	N	None	0	2.28822E-05	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
H/A	0.3962	ambiguous	0.5564	ambiguous	-0.412	Destabilizing	0.565	D	0.438	neutral	None	None	None	None	N
H/C	0.2574	likely_benign	0.3715	ambiguous	0.1	Stabilizing	0.996	D	0.619	neutral	None	None	None	None	N
H/D	0.3487	ambiguous	0.5538	ambiguous	0.037	Stabilizing	0.704	D	0.618	neutral	N	0.432991937	None	None	N
H/E	0.4303	ambiguous	0.619	pathogenic	0.094	Stabilizing	0.394	N	0.35	neutral	None	None	None	None	N
H/F	0.2904	likely_benign	0.3789	ambiguous	0.43	Stabilizing	0.986	D	0.671	prob.neutral	None	None	None	None	N
H/G	0.5393	ambiguous	0.6894	pathogenic	-0.73	Destabilizing	0.864	D	0.583	neutral	None	None	None	None	N
H/I	0.2957	likely_benign	0.4491	ambiguous	0.429	Stabilizing	0.986	D	0.685	prob.delet.	None	None	None	None	N
H/K	0.3696	ambiguous	0.5594	ambiguous	-0.348	Destabilizing	0.017	N	0.233	neutral	None	None	None	None	N
H/L	0.1362	likely_benign	0.2012	benign	0.429	Stabilizing	0.704	D	0.563	neutral	N	0.42896571	None	None	N
H/M	0.464	ambiguous	0.5662	pathogenic	0.264	Stabilizing	0.986	D	0.623	neutral	None	None	None	None	N
H/N	0.1193	likely_benign	0.204	benign	-0.339	Destabilizing	0.828	D	0.51	neutral	N	0.372476485	None	None	N
H/P	0.38	ambiguous	0.5261	ambiguous	0.173	Stabilizing	0.936	D	0.672	prob.neutral	N	0.433787844	None	None	N
H/Q	0.234	likely_benign	0.355	ambiguous	-0.19	Destabilizing	0.013	N	0.159	neutral	N	0.369747551	None	None	N
H/R	0.1836	likely_benign	0.3041	benign	-0.76	Destabilizing	0.329	N	0.473	neutral	N	0.40172281	None	None	N
H/S	0.2809	likely_benign	0.4074	ambiguous	-0.467	Destabilizing	0.565	D	0.492	neutral	None	None	None	None	N
H/T	0.33	likely_benign	0.4803	ambiguous	-0.304	Destabilizing	0.864	D	0.614	neutral	None	None	None	None	N
H/V	0.2592	likely_benign	0.3851	ambiguous	0.173	Stabilizing	0.864	D	0.65	prob.neutral	None	None	None	None	N
H/W	0.425	ambiguous	0.5026	ambiguous	0.626	Stabilizing	0.996	D	0.608	neutral	None	None	None	None	N
H/Y	0.098	likely_benign	0.1432	benign	0.834	Stabilizing	0.936	D	0.569	neutral	N	0.432023317	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.