TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16840	50743;50744;50745	chr2:178611791;178611790;178611789	chr2:179476518;179476517;179476516
N2AB	15199	45820;45821;45822	chr2:178611791;178611790;178611789	chr2:179476518;179476517;179476516
N2A	14272	43039;43040;43041	chr2:178611791;178611790;178611789	chr2:179476518;179476517;179476516
N2B	7775	23548;23549;23550	chr2:178611791;178611790;178611789	chr2:179476518;179476517;179476516
Novex-1	7900	23923;23924;23925	chr2:178611791;178611790;178611789	chr2:179476518;179476517;179476516
Novex-2	7967	24124;24125;24126	chr2:178611791;178611790;178611789	chr2:179476518;179476517;179476516
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Fn3-10
• Domain position: 90
• Structural Position: 123
• Q(SASA): 0.1855
• 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/A	None	None	0.539	N	0.709	0.255	0.226586394389	gnomAD-4.0.0	6.84674E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99868E-07	0	0
P/L	None	None	0.891	N	0.901	0.336	0.483891081108	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	0.2417	likely_benign	0.2629	benign	-1.187	Destabilizing	0.539	D	0.709	prob.delet.	N	0.471305467	None	None	N
P/C	0.9456	likely_pathogenic	0.9489	pathogenic	-0.776	Destabilizing	0.988	D	0.9	deleterious	None	None	None	None	N
P/D	0.9582	likely_pathogenic	0.9504	pathogenic	-0.789	Destabilizing	0.916	D	0.821	deleterious	None	None	None	None	N
P/E	0.872	likely_pathogenic	0.8685	pathogenic	-0.83	Destabilizing	0.844	D	0.82	deleterious	None	None	None	None	N
P/F	0.9672	likely_pathogenic	0.9661	pathogenic	-0.994	Destabilizing	0.988	D	0.91	deleterious	None	None	None	None	N
P/G	0.8319	likely_pathogenic	0.8588	pathogenic	-1.45	Destabilizing	0.607	D	0.796	deleterious	None	None	None	None	N
P/H	0.8866	likely_pathogenic	0.8739	pathogenic	-0.953	Destabilizing	0.984	D	0.851	deleterious	D	0.656543706	None	None	N
P/I	0.8582	likely_pathogenic	0.8601	pathogenic	-0.592	Destabilizing	0.916	D	0.906	deleterious	None	None	None	None	N
P/K	0.9302	likely_pathogenic	0.9153	pathogenic	-0.959	Destabilizing	0.844	D	0.807	deleterious	None	None	None	None	N
P/L	0.6672	likely_pathogenic	0.6456	pathogenic	-0.592	Destabilizing	0.891	D	0.901	deleterious	N	0.475992039	None	None	N
P/M	0.8478	likely_pathogenic	0.8519	pathogenic	-0.457	Destabilizing	0.996	D	0.858	deleterious	None	None	None	None	N
P/N	0.9191	likely_pathogenic	0.9211	pathogenic	-0.685	Destabilizing	0.844	D	0.882	deleterious	None	None	None	None	N
P/Q	0.7943	likely_pathogenic	0.7913	pathogenic	-0.89	Destabilizing	0.916	D	0.852	deleterious	None	None	None	None	N
P/R	0.8861	likely_pathogenic	0.8534	pathogenic	-0.418	Destabilizing	0.891	D	0.888	deleterious	D	0.655585495	None	None	N
P/S	0.6477	likely_pathogenic	0.6641	pathogenic	-1.177	Destabilizing	0.017	N	0.411	neutral	N	0.470099282	None	None	N
P/T	0.5837	likely_pathogenic	0.5995	pathogenic	-1.112	Destabilizing	0.804	D	0.786	deleterious	N	0.474944622	None	None	N
P/V	0.724	likely_pathogenic	0.7324	pathogenic	-0.754	Destabilizing	0.916	D	0.885	deleterious	None	None	None	None	N
P/W	0.9906	likely_pathogenic	0.9893	pathogenic	-1.121	Destabilizing	0.996	D	0.893	deleterious	None	None	None	None	N
P/Y	0.9651	likely_pathogenic	0.9624	pathogenic	-0.842	Destabilizing	0.988	D	0.91	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.