TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19340	58243;58244;58245	chr2:178594476;178594475;178594474	chr2:179459203;179459202;179459201
N2AB	17699	53320;53321;53322	chr2:178594476;178594475;178594474	chr2:179459203;179459202;179459201
N2A	16772	50539;50540;50541	chr2:178594476;178594475;178594474	chr2:179459203;179459202;179459201
N2B	10275	31048;31049;31050	chr2:178594476;178594475;178594474	chr2:179459203;179459202;179459201
Novex-1	10400	31423;31424;31425	chr2:178594476;178594475;178594474	chr2:179459203;179459202;179459201
Novex-2	10467	31624;31625;31626	chr2:178594476;178594475;178594474	chr2:179459203;179459202;179459201
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Fn3-28
• Domain position: 57
• Structural Position: 83
• Q(SASA): 0.662
• 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/H	rs777213118	-0.369	0.976	N	0.662	0.43	0.817808388354	gnomAD-2.1.1	7.14E-06	None	None	None	None	N	None	4.13E-05	0	None	0	0	None	0	None	0	7.81E-06	0
L/H	rs777213118	-0.369	0.976	N	0.662	0.43	0.817808388354	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/H	rs777213118	-0.369	0.976	N	0.662	0.43	0.817808388354	gnomAD-4.0.0	1.11575E-05	None	None	None	None	N	None	1.33526E-05	0	None	0	0	None	0	0	1.44121E-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	0.1994	likely_benign	0.2136	benign	-1.398	Destabilizing	0.25	N	0.575	neutral	None	None	None	None	N
L/C	0.4806	ambiguous	0.4976	ambiguous	-0.852	Destabilizing	0.982	D	0.64	neutral	None	None	None	None	N
L/D	0.5684	likely_pathogenic	0.5705	pathogenic	-0.612	Destabilizing	0.826	D	0.689	prob.neutral	None	None	None	None	N
L/E	0.312	likely_benign	0.3114	benign	-0.607	Destabilizing	0.826	D	0.693	prob.neutral	None	None	None	None	N
L/F	0.1647	likely_benign	0.159	benign	-0.905	Destabilizing	0.638	D	0.594	neutral	N	0.494161934	None	None	N
L/G	0.3815	ambiguous	0.3983	ambiguous	-1.709	Destabilizing	0.7	D	0.685	prob.neutral	None	None	None	None	N
L/H	0.2208	likely_benign	0.2147	benign	-0.792	Destabilizing	0.976	D	0.662	neutral	N	0.460164004	None	None	N
L/I	0.1028	likely_benign	0.099	benign	-0.63	Destabilizing	0.201	N	0.472	neutral	N	0.46993828	None	None	N
L/K	0.173	likely_benign	0.1762	benign	-0.893	Destabilizing	0.7	D	0.602	neutral	None	None	None	None	N
L/M	0.0915	likely_benign	0.1106	benign	-0.558	Destabilizing	0.009	N	0.171	neutral	None	None	None	None	N
L/N	0.2567	likely_benign	0.272	benign	-0.739	Destabilizing	0.826	D	0.689	prob.neutral	None	None	None	None	N
L/P	0.183	likely_benign	0.1704	benign	-0.854	Destabilizing	0.916	D	0.686	prob.neutral	N	0.425878072	None	None	N
L/Q	0.1264	likely_benign	0.1272	benign	-0.878	Destabilizing	0.7	D	0.67	neutral	None	None	None	None	N
L/R	0.1859	likely_benign	0.1785	benign	-0.324	Destabilizing	0.638	D	0.677	prob.neutral	N	0.406484235	None	None	N
L/S	0.212	likely_benign	0.2227	benign	-1.364	Destabilizing	0.7	D	0.586	neutral	None	None	None	None	N
L/T	0.1453	likely_benign	0.1548	benign	-1.235	Destabilizing	0.7	D	0.636	neutral	None	None	None	None	N
L/V	0.0937	likely_benign	0.0974	benign	-0.854	Destabilizing	0.094	N	0.507	neutral	N	0.441404885	None	None	N
L/W	0.3557	ambiguous	0.3173	benign	-0.951	Destabilizing	0.982	D	0.674	neutral	None	None	None	None	N
L/Y	0.3248	likely_benign	0.342	ambiguous	-0.731	Destabilizing	0.826	D	0.661	neutral	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.