TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3295	10108;10109;10110	chr2:178764632;178764631;178764630	chr2:179629359;179629358;179629357
N2AB	3295	10108;10109;10110	chr2:178764632;178764631;178764630	chr2:179629359;179629358;179629357
N2A	3295	10108;10109;10110	chr2:178764632;178764631;178764630	chr2:179629359;179629358;179629357
N2B	3249	9970;9971;9972	chr2:178764632;178764631;178764630	chr2:179629359;179629358;179629357
Novex-1	3249	9970;9971;9972	chr2:178764632;178764631;178764630	chr2:179629359;179629358;179629357
Novex-2	3249	9970;9971;9972	chr2:178764632;178764631;178764630	chr2:179629359;179629358;179629357
Novex-3	3295	10108;10109;10110	chr2:178764632;178764631;178764630	chr2:179629359;179629358;179629357

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACG
• RefSeq wild type template codon: TGC
• Domain: Ig-23
• Domain position: 57
• Structural Position: 137
• Q(SASA): 0.1273
• 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	rs145053177	-0.996	0.489	D	0.661	0.353	None	gnomAD-2.1.1	2.12E-05	None	None	None	None	N	None	2.40288E-04	0	None	0	0	None	0	None	0	0	0
T/A	rs145053177	-0.996	0.489	D	0.661	0.353	None	gnomAD-3.1.2	2.63E-05	None	None	None	None	N	None	9.66E-05	0	0	0	0	None	0	0	0	0	0
T/A	rs145053177	-0.996	0.489	D	0.661	0.353	None	gnomAD-4.0.0	4.95672E-06	None	None	None	None	N	None	1.06806E-04	0	None	0	0	None	0	0	0	0	0
T/M	rs191708454	-0.147	0.843	D	0.627	0.461	None	gnomAD-2.1.1	2.54923E-04	None	None	None	None	N	None	0	1.73561E-04	None	0	5.45E-05	None	1.79656E-03	None	0	1.76E-05	0
T/M	rs191708454	-0.147	0.843	D	0.627	0.461	None	gnomAD-3.1.2	7.23E-05	None	None	None	None	N	None	2.42E-05	6.55E-05	0	0	0	None	0	0	2.94E-05	1.24481E-03	4.78469E-04
T/M	rs191708454	-0.147	0.843	D	0.627	0.461	None	1000 genomes	3.99361E-04	None	None	None	None	N	None	0	1.4E-03	None	None	0	0	None	None	None	1E-03	None
T/M	rs191708454	-0.147	0.843	D	0.627	0.461	None	gnomAD-4.0.0	1.08423E-04	None	None	None	None	N	None	1.33326E-05	1.16647E-04	None	0	0	None	1.56167E-05	3.3036E-04	1.44068E-05	1.52626E-03	1.27992E-04
T/P	rs145053177	None	0.97	D	0.752	0.577	0.598497351524	gnomAD-4.0.0	6.84071E-07	None	None	None	None	N	None	0	2.23624E-05	None	0	0	None	0	0	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
T/A	0.3095	likely_benign	0.458	ambiguous	-0.964	Destabilizing	0.489	N	0.661	neutral	D	0.558565744	None	None	N
T/C	0.704	likely_pathogenic	0.7769	pathogenic	-0.669	Destabilizing	0.998	D	0.726	prob.delet.	None	None	None	None	N
T/D	0.9414	likely_pathogenic	0.9652	pathogenic	-1.691	Destabilizing	0.86	D	0.725	prob.delet.	None	None	None	None	N
T/E	0.8426	likely_pathogenic	0.889	pathogenic	-1.445	Destabilizing	0.754	D	0.719	prob.delet.	None	None	None	None	N
T/F	0.7493	likely_pathogenic	0.8455	pathogenic	-0.51	Destabilizing	0.956	D	0.765	deleterious	None	None	None	None	N
T/G	0.79	likely_pathogenic	0.8557	pathogenic	-1.411	Destabilizing	0.86	D	0.742	deleterious	None	None	None	None	N
T/H	0.6502	likely_pathogenic	0.7581	pathogenic	-1.561	Destabilizing	0.994	D	0.76	deleterious	None	None	None	None	N
T/I	0.5364	ambiguous	0.7019	pathogenic	0.225	Stabilizing	0.915	D	0.751	deleterious	None	None	None	None	N
T/K	0.7576	likely_pathogenic	0.8717	pathogenic	-0.4	Destabilizing	0.855	D	0.728	prob.delet.	D	0.590934058	None	None	N
T/L	0.352	ambiguous	0.5015	ambiguous	0.225	Stabilizing	0.514	D	0.695	prob.neutral	None	None	None	None	N
T/M	0.1915	likely_benign	0.3129	benign	0.028	Stabilizing	0.843	D	0.627	neutral	D	0.663511483	None	None	N
T/N	0.5719	likely_pathogenic	0.7052	pathogenic	-1.258	Destabilizing	0.956	D	0.688	prob.neutral	None	None	None	None	N
T/P	0.9073	likely_pathogenic	0.958	pathogenic	-0.141	Destabilizing	0.97	D	0.752	deleterious	D	0.679219875	None	None	N
T/Q	0.6092	likely_pathogenic	0.7158	pathogenic	-0.877	Destabilizing	0.356	N	0.567	neutral	None	None	None	None	N
T/R	0.6648	likely_pathogenic	0.8192	pathogenic	-0.813	Destabilizing	0.976	D	0.746	deleterious	D	0.568348806	None	None	N
T/S	0.3099	likely_benign	0.4314	ambiguous	-1.405	Destabilizing	0.153	N	0.48	neutral	N	0.49322956	None	None	N
T/V	0.3814	ambiguous	0.4979	ambiguous	-0.141	Destabilizing	0.754	D	0.683	prob.neutral	None	None	None	None	N
T/W	0.9165	likely_pathogenic	0.9432	pathogenic	-0.831	Destabilizing	0.998	D	0.765	deleterious	None	None	None	None	N
T/Y	0.7518	likely_pathogenic	0.8247	pathogenic	-0.376	Destabilizing	0.978	D	0.766	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.