TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29934	90025;90026;90027	chr2:178553100;178553099;178553098	chr2:179417827;179417826;179417825
N2AB	28293	85102;85103;85104	chr2:178553100;178553099;178553098	chr2:179417827;179417826;179417825
N2A	27366	82321;82322;82323	chr2:178553100;178553099;178553098	chr2:179417827;179417826;179417825
N2B	20869	62830;62831;62832	chr2:178553100;178553099;178553098	chr2:179417827;179417826;179417825
Novex-1	20994	63205;63206;63207	chr2:178553100;178553099;178553098	chr2:179417827;179417826;179417825
Novex-2	21061	63406;63407;63408	chr2:178553100;178553099;178553098	chr2:179417827;179417826;179417825
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-106
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.1047
• 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
P/L	None	None	1.0	D	0.85	0.578	0.75932986891	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
P/A	0.8888	likely_pathogenic	0.8025	pathogenic	-1.595	Destabilizing	0.999	D	0.844	deleterious	D	0.545507325	None	None	N
P/C	0.9965	likely_pathogenic	0.9935	pathogenic	-1.985	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
P/D	0.9996	likely_pathogenic	0.9993	pathogenic	-3.132	Highly Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
P/E	0.9988	likely_pathogenic	0.9982	pathogenic	-3.078	Highly Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
P/F	0.9998	likely_pathogenic	0.9996	pathogenic	-1.191	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
P/G	0.9944	likely_pathogenic	0.9904	pathogenic	-1.908	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
P/H	0.9986	likely_pathogenic	0.9978	pathogenic	-1.275	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
P/I	0.9964	likely_pathogenic	0.9944	pathogenic	-0.792	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
P/K	0.9991	likely_pathogenic	0.9986	pathogenic	-1.47	Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	N
P/L	0.983	likely_pathogenic	0.9721	pathogenic	-0.792	Destabilizing	1.0	D	0.85	deleterious	D	0.535418467	None	None	N
P/M	0.998	likely_pathogenic	0.9966	pathogenic	-1.045	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
P/N	0.9992	likely_pathogenic	0.9988	pathogenic	-1.734	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
P/Q	0.9976	likely_pathogenic	0.996	pathogenic	-1.924	Destabilizing	1.0	D	0.84	deleterious	D	0.546267793	None	None	N
P/R	0.9962	likely_pathogenic	0.9941	pathogenic	-0.972	Destabilizing	1.0	D	0.861	deleterious	D	0.546014304	None	None	N
P/S	0.984	likely_pathogenic	0.9668	pathogenic	-2.089	Highly Destabilizing	1.0	D	0.793	deleterious	D	0.545000346	None	None	N
P/T	0.9846	likely_pathogenic	0.9725	pathogenic	-1.933	Destabilizing	1.0	D	0.801	deleterious	D	0.546014304	None	None	N
P/V	0.9834	likely_pathogenic	0.9743	pathogenic	-1.032	Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	N
P/W	0.9999	likely_pathogenic	0.9999	pathogenic	-1.463	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
P/Y	0.9997	likely_pathogenic	0.9996	pathogenic	-1.131	Destabilizing	1.0	D	0.851	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.