TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2100	6523;6524;6525	chr2:178775566;178775565;178775564	chr2:179640293;179640292;179640291
N2AB	2100	6523;6524;6525	chr2:178775566;178775565;178775564	chr2:179640293;179640292;179640291
N2A	2100	6523;6524;6525	chr2:178775566;178775565;178775564	chr2:179640293;179640292;179640291
N2B	2054	6385;6386;6387	chr2:178775566;178775565;178775564	chr2:179640293;179640292;179640291
Novex-1	2054	6385;6386;6387	chr2:178775566;178775565;178775564	chr2:179640293;179640292;179640291
Novex-2	2054	6385;6386;6387	chr2:178775566;178775565;178775564	chr2:179640293;179640292;179640291
Novex-3	2100	6523;6524;6525	chr2:178775566;178775565;178775564	chr2:179640293;179640292;179640291

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Ig-10
• Domain position: 23
• Structural Position: 34
• Q(SASA): 0.1797
• 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
R/I	None	None	1.0	D	0.769	0.59	0.761427779387	gnomAD-4.0.0	1.59069E-06	None	None	None	None	N	None	0	0	None	0	2.775E-05	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
R/A	0.9184	likely_pathogenic	0.9256	pathogenic	-1.47	Destabilizing	0.999	D	0.599	neutral	None	None	None	None	N
R/C	0.6569	likely_pathogenic	0.6719	pathogenic	-1.57	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
R/D	0.9848	likely_pathogenic	0.9862	pathogenic	-0.616	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
R/E	0.8928	likely_pathogenic	0.903	pathogenic	-0.427	Destabilizing	0.999	D	0.584	neutral	None	None	None	None	N
R/F	0.9601	likely_pathogenic	0.9622	pathogenic	-0.876	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
R/G	0.8938	likely_pathogenic	0.9046	pathogenic	-1.815	Destabilizing	1.0	D	0.745	deleterious	D	0.561514846	None	None	N
R/H	0.345	ambiguous	0.3776	ambiguous	-1.801	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
R/I	0.8578	likely_pathogenic	0.856	pathogenic	-0.495	Destabilizing	1.0	D	0.769	deleterious	D	0.542211438	None	None	N
R/K	0.2752	likely_benign	0.2794	benign	-1.294	Destabilizing	0.997	D	0.45	neutral	N	0.493529302	None	None	N
R/L	0.7605	likely_pathogenic	0.7773	pathogenic	-0.495	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
R/M	0.8549	likely_pathogenic	0.8623	pathogenic	-1.012	Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	N
R/N	0.9616	likely_pathogenic	0.9631	pathogenic	-1.063	Destabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	N
R/P	0.991	likely_pathogenic	0.9927	pathogenic	-0.804	Destabilizing	1.0	D	0.758	deleterious	None	None	None	None	N
R/Q	0.3328	likely_benign	0.3604	ambiguous	-1.001	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
R/S	0.9433	likely_pathogenic	0.948	pathogenic	-1.896	Destabilizing	1.0	D	0.764	deleterious	N	0.507788882	None	None	N
R/T	0.8466	likely_pathogenic	0.8544	pathogenic	-1.504	Destabilizing	1.0	D	0.751	deleterious	N	0.481099561	None	None	N
R/V	0.864	likely_pathogenic	0.8677	pathogenic	-0.804	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
R/W	0.7215	likely_pathogenic	0.7396	pathogenic	-0.443	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
R/Y	0.9095	likely_pathogenic	0.9145	pathogenic	-0.217	Destabilizing	1.0	D	0.783	deleterious	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.