TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13803	41632;41633;41634	chr2:178636164;178636163;178636162	chr2:179500891;179500890;179500889
N2AB	12162	36709;36710;36711	chr2:178636164;178636163;178636162	chr2:179500891;179500890;179500889
N2A	11235	33928;33929;33930	chr2:178636164;178636163;178636162	chr2:179500891;179500890;179500889
N2B	4738	14437;14438;14439	chr2:178636164;178636163;178636162	chr2:179500891;179500890;179500889
Novex-1	4863	14812;14813;14814	chr2:178636164;178636163;178636162	chr2:179500891;179500890;179500889
Novex-2	4930	15013;15014;15015	chr2:178636164;178636163;178636162	chr2:179500891;179500890;179500889
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-88
• Domain position: 24
• Structural Position: 34
• Q(SASA): 0.3015
• 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/Q	None	None	1.0	N	0.626	0.29	0.15556083564	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	0	6.5189E-04	None	0	None	0	0	0
E/Q	None	None	1.0	N	0.626	0.29	0.15556083564	gnomAD-4.0.0	1.59369E-06	None	None	None	None	N	None	0	0	None	0	2.7922E-05	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
E/A	0.5285	ambiguous	0.6547	pathogenic	-1.036	Destabilizing	0.999	D	0.78	deleterious	N	0.410441379	None	None	N
E/C	0.976	likely_pathogenic	0.9847	pathogenic	-0.652	Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	N
E/D	0.7704	likely_pathogenic	0.8332	pathogenic	-1.379	Destabilizing	0.999	D	0.641	neutral	N	0.35087159	None	None	N
E/F	0.9562	likely_pathogenic	0.9737	pathogenic	-0.578	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
E/G	0.7493	likely_pathogenic	0.8435	pathogenic	-1.43	Destabilizing	1.0	D	0.749	deleterious	N	0.390562713	None	None	N
E/H	0.8979	likely_pathogenic	0.9367	pathogenic	-0.934	Destabilizing	1.0	D	0.685	prob.delet.	None	None	None	None	N
E/I	0.7147	likely_pathogenic	0.7986	pathogenic	0.058	Stabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
E/K	0.5749	likely_pathogenic	0.7363	pathogenic	-1.058	Destabilizing	1.0	D	0.7	prob.delet.	N	0.345272507	None	None	N
E/L	0.836	likely_pathogenic	0.8942	pathogenic	0.058	Stabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
E/M	0.7897	likely_pathogenic	0.8594	pathogenic	0.64	Stabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
E/N	0.8647	likely_pathogenic	0.9145	pathogenic	-1.443	Destabilizing	1.0	D	0.671	prob.neutral	None	None	None	None	N
E/P	0.9929	likely_pathogenic	0.9958	pathogenic	-0.286	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
E/Q	0.3356	likely_benign	0.4354	ambiguous	-1.278	Destabilizing	1.0	D	0.626	neutral	N	0.35330971	None	None	N
E/R	0.7126	likely_pathogenic	0.8227	pathogenic	-0.827	Destabilizing	1.0	D	0.67	prob.neutral	None	None	None	None	N
E/S	0.6498	likely_pathogenic	0.7371	pathogenic	-1.879	Destabilizing	0.999	D	0.691	prob.delet.	None	None	None	None	N
E/T	0.6219	likely_pathogenic	0.7114	pathogenic	-1.546	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
E/V	0.5214	ambiguous	0.6272	pathogenic	-0.286	Destabilizing	1.0	D	0.797	deleterious	N	0.323193806	None	None	N
E/W	0.9915	likely_pathogenic	0.9947	pathogenic	-0.426	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
E/Y	0.9381	likely_pathogenic	0.9603	pathogenic	-0.355	Destabilizing	1.0	D	0.886	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.