TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25709	77350;77351;77352	chr2:178569007;178569006;178569005	chr2:179433734;179433733;179433732
N2AB	24068	72427;72428;72429	chr2:178569007;178569006;178569005	chr2:179433734;179433733;179433732
N2A	23141	69646;69647;69648	chr2:178569007;178569006;178569005	chr2:179433734;179433733;179433732
N2B	16644	50155;50156;50157	chr2:178569007;178569006;178569005	chr2:179433734;179433733;179433732
Novex-1	16769	50530;50531;50532	chr2:178569007;178569006;178569005	chr2:179433734;179433733;179433732
Novex-2	16836	50731;50732;50733	chr2:178569007;178569006;178569005	chr2:179433734;179433733;179433732
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-75
• Domain position: 12
• Structural Position: 14
• Q(SASA): 0.4351
• 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
D/A	rs1707103269	None	1.0	N	0.735	0.556	0.467247493403	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	2.88184E-04	0	None	0	0	0	0	0
D/A	rs1707103269	None	1.0	N	0.735	0.556	0.467247493403	gnomAD-4.0.0	6.57549E-06	None	None	None	None	N	None	0	0	None	2.88184E-04	0	None	0	0	0	0	0
D/H	rs772757849	-0.418	1.0	N	0.666	0.517	0.360565625551	gnomAD-2.1.1	1.43E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	3.13E-05	0
D/H	rs772757849	-0.418	1.0	N	0.666	0.517	0.360565625551	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
D/H	rs772757849	-0.418	1.0	N	0.666	0.517	0.360565625551	gnomAD-4.0.0	8.67806E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.18689E-05	0	0
D/V	rs1707103269	None	1.0	N	0.773	0.645	0.690481662768	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
D/V	rs1707103269	None	1.0	N	0.773	0.645	0.690481662768	gnomAD-4.0.0	6.57549E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47119E-05	0	0
D/Y	rs772757849	-0.085	1.0	N	0.698	0.526	0.723653669168	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	5.58E-05	None	0	None	0	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
D/A	0.5426	ambiguous	0.476	ambiguous	-0.484	Destabilizing	1.0	D	0.735	prob.delet.	N	0.479091012	None	None	N
D/C	0.9386	likely_pathogenic	0.9176	pathogenic	0.065	Stabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	N
D/E	0.505	ambiguous	0.4486	ambiguous	-0.427	Destabilizing	0.994	D	0.395	neutral	N	0.475285385	None	None	N
D/F	0.9248	likely_pathogenic	0.8955	pathogenic	-0.439	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
D/G	0.5506	ambiguous	0.5059	ambiguous	-0.719	Destabilizing	1.0	D	0.731	prob.delet.	N	0.489815434	None	None	N
D/H	0.741	likely_pathogenic	0.6742	pathogenic	-0.545	Destabilizing	1.0	D	0.666	neutral	N	0.4985913	None	None	N
D/I	0.8492	likely_pathogenic	0.7961	pathogenic	0.1	Stabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
D/K	0.8485	likely_pathogenic	0.8053	pathogenic	0.236	Stabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
D/L	0.8242	likely_pathogenic	0.7874	pathogenic	0.1	Stabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
D/M	0.911	likely_pathogenic	0.8908	pathogenic	0.443	Stabilizing	1.0	D	0.692	prob.neutral	None	None	None	None	N
D/N	0.2339	likely_benign	0.1928	benign	-0.119	Destabilizing	1.0	D	0.653	neutral	D	0.522847258	None	None	N
D/P	0.9948	likely_pathogenic	0.9916	pathogenic	-0.072	Destabilizing	0.998	D	0.76	deleterious	None	None	None	None	N
D/Q	0.792	likely_pathogenic	0.7507	pathogenic	-0.078	Destabilizing	1.0	D	0.7	prob.neutral	None	None	None	None	N
D/R	0.84	likely_pathogenic	0.7958	pathogenic	0.284	Stabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	N
D/S	0.3764	ambiguous	0.3157	benign	-0.246	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	N
D/T	0.6233	likely_pathogenic	0.5612	ambiguous	-0.056	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
D/V	0.6917	likely_pathogenic	0.6117	pathogenic	-0.072	Destabilizing	1.0	D	0.773	deleterious	N	0.500944704	None	None	N
D/W	0.9878	likely_pathogenic	0.9829	pathogenic	-0.283	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	N
D/Y	0.7033	likely_pathogenic	0.6163	pathogenic	-0.192	Destabilizing	1.0	D	0.698	prob.neutral	N	0.509947606	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.