TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21750	65473;65474;65475	chr2:178584303;178584302;178584301	chr2:179449030;179449029;179449028
N2AB	20109	60550;60551;60552	chr2:178584303;178584302;178584301	chr2:179449030;179449029;179449028
N2A	19182	57769;57770;57771	chr2:178584303;178584302;178584301	chr2:179449030;179449029;179449028
N2B	12685	38278;38279;38280	chr2:178584303;178584302;178584301	chr2:179449030;179449029;179449028
Novex-1	12810	38653;38654;38655	chr2:178584303;178584302;178584301	chr2:179449030;179449029;179449028
Novex-2	12877	38854;38855;38856	chr2:178584303;178584302;178584301	chr2:179449030;179449029;179449028
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-45
• Domain position: 92
• Structural Position: 125
• Q(SASA): 0.8476
• 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
E/A	rs761034547	0.185	0.799	N	0.579	0.229	0.300110245524	gnomAD-2.1.1	4.24E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.58E-05	None	0	0	0
E/A	rs761034547	0.185	0.799	N	0.579	0.229	0.300110245524	gnomAD-4.0.0	1.64996E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.49522E-05	0
E/K	None	None	0.799	N	0.617	0.234	0.278143212241	gnomAD-4.0.0	6.59988E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.92692E-06	1.4958E-05	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
E/A	0.1743	likely_benign	0.141	benign	-0.247	Destabilizing	0.799	D	0.579	neutral	N	0.469844166	None	None	N
E/C	0.8949	likely_pathogenic	0.8398	pathogenic	-0.223	Destabilizing	0.998	D	0.787	deleterious	None	None	None	None	N
E/D	0.1023	likely_benign	0.0843	benign	-0.258	Destabilizing	0.002	N	0.168	neutral	N	0.480440489	None	None	N
E/F	0.897	likely_pathogenic	0.842	pathogenic	-0.067	Destabilizing	0.991	D	0.731	deleterious	None	None	None	None	N
E/G	0.2251	likely_benign	0.1673	benign	-0.407	Destabilizing	0.799	D	0.577	neutral	N	0.476213722	None	None	N
E/H	0.6467	likely_pathogenic	0.5535	ambiguous	0.451	Stabilizing	0.991	D	0.588	neutral	None	None	None	None	N
E/I	0.541	ambiguous	0.4456	ambiguous	0.133	Stabilizing	0.974	D	0.741	deleterious	None	None	None	None	N
E/K	0.2844	likely_benign	0.2173	benign	0.406	Stabilizing	0.799	D	0.617	neutral	N	0.470858124	None	None	N
E/L	0.5844	likely_pathogenic	0.4971	ambiguous	0.133	Stabilizing	0.974	D	0.716	prob.delet.	None	None	None	None	N
E/M	0.6563	likely_pathogenic	0.5662	pathogenic	0.013	Stabilizing	0.998	D	0.748	deleterious	None	None	None	None	N
E/N	0.2872	likely_benign	0.2154	benign	-0.042	Destabilizing	0.725	D	0.604	neutral	None	None	None	None	N
E/P	0.3673	ambiguous	0.3126	benign	0.025	Stabilizing	0.974	D	0.616	neutral	None	None	None	None	N
E/Q	0.2137	likely_benign	0.1797	benign	0.018	Stabilizing	0.89	D	0.609	neutral	N	0.472655323	None	None	N
E/R	0.4212	ambiguous	0.3349	benign	0.677	Stabilizing	0.974	D	0.627	neutral	None	None	None	None	N
E/S	0.2263	likely_benign	0.1768	benign	-0.157	Destabilizing	0.841	D	0.583	neutral	None	None	None	None	N
E/T	0.2994	likely_benign	0.2359	benign	-0.009	Destabilizing	0.841	D	0.606	neutral	None	None	None	None	N
E/V	0.3369	likely_benign	0.2708	benign	0.025	Stabilizing	0.966	D	0.659	prob.neutral	N	0.481592092	None	None	N
E/W	0.9594	likely_pathogenic	0.9287	pathogenic	0.079	Stabilizing	0.998	D	0.805	deleterious	None	None	None	None	N
E/Y	0.7901	likely_pathogenic	0.6892	pathogenic	0.174	Stabilizing	0.991	D	0.747	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.