TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20701	62326;62327;62328	chr2:178589624;178589623;178589622	chr2:179454351;179454350;179454349
N2AB	19060	57403;57404;57405	chr2:178589624;178589623;178589622	chr2:179454351;179454350;179454349
N2A	18133	54622;54623;54624	chr2:178589624;178589623;178589622	chr2:179454351;179454350;179454349
N2B	11636	35131;35132;35133	chr2:178589624;178589623;178589622	chr2:179454351;179454350;179454349
Novex-1	11761	35506;35507;35508	chr2:178589624;178589623;178589622	chr2:179454351;179454350;179454349
Novex-2	11828	35707;35708;35709	chr2:178589624;178589623;178589622	chr2:179454351;179454350;179454349
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Fn3-38
• Domain position: 34
• Structural Position: 36
• Q(SASA): 0.5311
• 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
L/Q	rs1383995916	None	1.0	N	0.796	0.428	0.73673398233	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
L/Q	rs1383995916	None	1.0	N	0.796	0.428	0.73673398233	gnomAD-4.0.0	6.57549E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47111E-05	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
L/A	0.4771	ambiguous	0.4387	ambiguous	-0.935	Destabilizing	0.998	D	0.654	neutral	None	None	None	None	N
L/C	0.7492	likely_pathogenic	0.7205	pathogenic	-0.502	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
L/D	0.8936	likely_pathogenic	0.852	pathogenic	-0.552	Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	N
L/E	0.6164	likely_pathogenic	0.5551	ambiguous	-0.648	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
L/F	0.3145	likely_benign	0.31	benign	-0.937	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
L/G	0.8276	likely_pathogenic	0.7936	pathogenic	-1.131	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
L/H	0.4731	ambiguous	0.4164	ambiguous	-0.416	Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
L/I	0.0891	likely_benign	0.0766	benign	-0.53	Destabilizing	0.813	D	0.197	neutral	None	None	None	None	N
L/K	0.4236	ambiguous	0.4086	ambiguous	-0.484	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
L/M	0.1564	likely_benign	0.1667	benign	-0.312	Destabilizing	0.999	D	0.708	prob.delet.	N	0.502363509	None	None	N
L/N	0.593	likely_pathogenic	0.4934	ambiguous	-0.152	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
L/P	0.9503	likely_pathogenic	0.9421	pathogenic	-0.632	Destabilizing	1.0	D	0.813	deleterious	N	0.502363509	None	None	N
L/Q	0.2969	likely_benign	0.2622	benign	-0.447	Destabilizing	1.0	D	0.796	deleterious	N	0.499741112	None	None	N
L/R	0.4043	ambiguous	0.3775	ambiguous	0.161	Stabilizing	1.0	D	0.815	deleterious	N	0.510688825	None	None	N
L/S	0.5735	likely_pathogenic	0.4935	ambiguous	-0.618	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
L/T	0.3171	likely_benign	0.2539	benign	-0.608	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
L/V	0.1123	likely_benign	0.1055	benign	-0.632	Destabilizing	0.981	D	0.471	neutral	N	0.521847181	None	None	N
L/W	0.6413	likely_pathogenic	0.6228	pathogenic	-0.928	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
L/Y	0.5864	likely_pathogenic	0.5895	pathogenic	-0.692	Destabilizing	1.0	D	0.798	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.