TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16940	51043;51044;51045	chr2:178611411;178611410;178611409	chr2:179476138;179476137;179476136
N2AB	15299	46120;46121;46122	chr2:178611411;178611410;178611409	chr2:179476138;179476137;179476136
N2A	14372	43339;43340;43341	chr2:178611411;178611410;178611409	chr2:179476138;179476137;179476136
N2B	7875	23848;23849;23850	chr2:178611411;178611410;178611409	chr2:179476138;179476137;179476136
Novex-1	8000	24223;24224;24225	chr2:178611411;178611410;178611409	chr2:179476138;179476137;179476136
Novex-2	8067	24424;24425;24426	chr2:178611411;178611410;178611409	chr2:179476138;179476137;179476136
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Fn3-11
• Domain position: 89
• Structural Position: 121
• Q(SASA): 0.1531
• 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
S/P	None	None	1.0	D	0.884	0.756	0.589372124375	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
S/A	0.1333	likely_benign	0.3531	ambiguous	-0.85	Destabilizing	0.997	D	0.856	deleterious	D	0.620080833	None	None	N
S/C	0.2164	likely_benign	0.5841	pathogenic	-0.869	Destabilizing	1.0	D	0.881	deleterious	D	0.783126503	None	None	N
S/D	0.9572	likely_pathogenic	0.9877	pathogenic	-1.441	Destabilizing	0.999	D	0.899	deleterious	None	None	None	None	N
S/E	0.9643	likely_pathogenic	0.9905	pathogenic	-1.323	Destabilizing	0.999	D	0.899	deleterious	None	None	None	None	N
S/F	0.9095	likely_pathogenic	0.9869	pathogenic	-0.572	Destabilizing	1.0	D	0.921	deleterious	D	0.783126503	None	None	N
S/G	0.2168	likely_benign	0.365	ambiguous	-1.183	Destabilizing	0.999	D	0.897	deleterious	None	None	None	None	N
S/H	0.9293	likely_pathogenic	0.9866	pathogenic	-1.532	Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	N
S/I	0.7975	likely_pathogenic	0.9678	pathogenic	-0.029	Destabilizing	1.0	D	0.904	deleterious	None	None	None	None	N
S/K	0.9873	likely_pathogenic	0.998	pathogenic	-0.875	Destabilizing	0.999	D	0.895	deleterious	None	None	None	None	N
S/L	0.5392	ambiguous	0.8508	pathogenic	-0.029	Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	N
S/M	0.7087	likely_pathogenic	0.92	pathogenic	-0.123	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
S/N	0.7894	likely_pathogenic	0.9292	pathogenic	-1.215	Destabilizing	0.999	D	0.905	deleterious	None	None	None	None	N
S/P	0.9748	likely_pathogenic	0.9915	pathogenic	-0.269	Destabilizing	1.0	D	0.884	deleterious	D	0.783058568	None	None	N
S/Q	0.9357	likely_pathogenic	0.9859	pathogenic	-1.152	Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
S/R	0.9665	likely_pathogenic	0.9948	pathogenic	-0.982	Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	N
S/T	0.2352	likely_benign	0.4467	ambiguous	-0.977	Destabilizing	0.999	D	0.905	deleterious	D	0.622883572	None	None	N
S/V	0.632	likely_pathogenic	0.9345	pathogenic	-0.269	Destabilizing	1.0	D	0.908	deleterious	None	None	None	None	N
S/W	0.9459	likely_pathogenic	0.9905	pathogenic	-0.737	Destabilizing	1.0	D	0.919	deleterious	None	None	None	None	N
S/Y	0.8948	likely_pathogenic	0.9832	pathogenic	-0.391	Destabilizing	1.0	D	0.917	deleterious	D	0.783058568	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.