TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18892	56899;56900;56901	chr2:178599036;178599035;178599034	chr2:179463763;179463762;179463761
N2AB	17251	51976;51977;51978	chr2:178599036;178599035;178599034	chr2:179463763;179463762;179463761
N2A	16324	49195;49196;49197	chr2:178599036;178599035;178599034	chr2:179463763;179463762;179463761
N2B	9827	29704;29705;29706	chr2:178599036;178599035;178599034	chr2:179463763;179463762;179463761
Novex-1	9952	30079;30080;30081	chr2:178599036;178599035;178599034	chr2:179463763;179463762;179463761
Novex-2	10019	30280;30281;30282	chr2:178599036;178599035;178599034	chr2:179463763;179463762;179463761
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-25
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.3794
• 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
T/A	rs780258242	-0.8	0.898	N	0.494	0.23	0.255777322467	gnomAD-2.1.1	4.52E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.99E-05	None	0	0	0
T/A	rs780258242	-0.8	0.898	N	0.494	0.23	0.255777322467	gnomAD-4.0.0	7.00877E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.24076E-05	0
T/I	None	None	0.997	N	0.818	0.417	0.37479162749	gnomAD-4.0.0	6.99567E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.124E-07	0	0
T/K	rs1405285641	None	0.993	N	0.743	0.365	0.341934017632	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	6.57E-05	0	0	0	None	0	0	0	0	0
T/K	rs1405285641	None	0.993	N	0.743	0.365	0.341934017632	gnomAD-4.0.0	1.26472E-06	None	None	None	None	N	None	0	1.82375E-05	None	0	0	None	0	0	0	0	1.63848E-05
T/P	rs780258242	-0.362	0.997	N	0.822	0.422	0.375326005269	gnomAD-2.1.1	1.81E-05	None	None	None	None	N	None	2.70709E-04	0	None	0	0	None	0	None	0	0	0
T/P	rs780258242	-0.362	0.997	N	0.822	0.422	0.375326005269	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	0	1.31337E-04	0	0	0	None	0	0	0	0	0
T/P	rs780258242	-0.362	0.997	N	0.822	0.422	0.375326005269	gnomAD-4.0.0	6.33354E-06	None	None	None	None	N	None	6.80087E-05	7.4118E-05	None	0	0	None	0	0	0	0	1.6408E-05
T/R	rs1405285641	-0.147	0.993	N	0.82	0.375	0.403752378121	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.49E-05	0
T/R	rs1405285641	-0.147	0.993	N	0.82	0.375	0.403752378121	gnomAD-4.0.0	5.59653E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.2992E-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
T/A	0.0888	likely_benign	0.0909	benign	-0.563	Destabilizing	0.898	D	0.494	neutral	N	0.512441051	None	None	N
T/C	0.4208	ambiguous	0.4039	ambiguous	-0.38	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	N
T/D	0.5001	ambiguous	0.4737	ambiguous	-0.061	Destabilizing	0.995	D	0.745	deleterious	None	None	None	None	N
T/E	0.3273	likely_benign	0.2885	benign	-0.101	Destabilizing	0.995	D	0.731	prob.delet.	None	None	None	None	N
T/F	0.2628	likely_benign	0.2593	benign	-0.822	Destabilizing	0.999	D	0.849	deleterious	None	None	None	None	N
T/G	0.2955	likely_benign	0.3065	benign	-0.766	Destabilizing	0.966	D	0.641	neutral	None	None	None	None	N
T/H	0.307	likely_benign	0.2808	benign	-1.083	Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	N
T/I	0.16	likely_benign	0.1457	benign	-0.133	Destabilizing	0.997	D	0.818	deleterious	N	0.506227154	None	None	N
T/K	0.2993	likely_benign	0.2524	benign	-0.605	Destabilizing	0.993	D	0.743	deleterious	N	0.485137019	None	None	N
T/L	0.1201	likely_benign	0.1179	benign	-0.133	Destabilizing	0.983	D	0.628	neutral	None	None	None	None	N
T/M	0.1033	likely_benign	0.1039	benign	0.073	Stabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
T/N	0.1782	likely_benign	0.176	benign	-0.452	Destabilizing	0.995	D	0.675	neutral	None	None	None	None	N
T/P	0.6969	likely_pathogenic	0.6669	pathogenic	-0.245	Destabilizing	0.997	D	0.822	deleterious	N	0.499440674	None	None	N
T/Q	0.2477	likely_benign	0.2264	benign	-0.654	Destabilizing	0.998	D	0.83	deleterious	None	None	None	None	N
T/R	0.2567	likely_benign	0.2218	benign	-0.337	Destabilizing	0.993	D	0.82	deleterious	N	0.481155352	None	None	N
T/S	0.116	likely_benign	0.1206	benign	-0.676	Destabilizing	0.362	N	0.347	neutral	N	0.502029269	None	None	N
T/V	0.1166	likely_benign	0.109	benign	-0.245	Destabilizing	0.983	D	0.541	neutral	None	None	None	None	N
T/W	0.6514	likely_pathogenic	0.6227	pathogenic	-0.786	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
T/Y	0.3261	likely_benign	0.2979	benign	-0.537	Destabilizing	0.999	D	0.847	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.