TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25326	76201;76202;76203	chr2:178570156;178570155;178570154	chr2:179434883;179434882;179434881
N2AB	23685	71278;71279;71280	chr2:178570156;178570155;178570154	chr2:179434883;179434882;179434881
N2A	22758	68497;68498;68499	chr2:178570156;178570155;178570154	chr2:179434883;179434882;179434881
N2B	16261	49006;49007;49008	chr2:178570156;178570155;178570154	chr2:179434883;179434882;179434881
Novex-1	16386	49381;49382;49383	chr2:178570156;178570155;178570154	chr2:179434883;179434882;179434881
Novex-2	16453	49582;49583;49584	chr2:178570156;178570155;178570154	chr2:179434883;179434882;179434881
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: Fn3-72
• Domain position: 23
• Structural Position: 25
• Q(SASA): 0.5218
• 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/G	rs767430531	-0.857	0.014	N	0.333	0.191	0.275215494804	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.93E-06	0
E/G	rs767430531	-0.857	0.014	N	0.333	0.191	0.275215494804	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	2.94E-05	0	0
E/G	rs767430531	-0.857	0.014	N	0.333	0.191	0.275215494804	gnomAD-4.0.0	1.17765E-05	None	None	None	None	N	None	1.33554E-05	0	None	0	0	None	0	0	1.44114E-05	0	1.60154E-05

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	0.1433	likely_benign	0.1557	benign	-0.35	Destabilizing	0.822	D	0.584	neutral	N	0.474461453	None	None	N
E/C	0.7244	likely_pathogenic	0.7693	pathogenic	-0.291	Destabilizing	0.998	D	0.775	deleterious	None	None	None	None	N
E/D	0.1007	likely_benign	0.1281	benign	-0.659	Destabilizing	0.006	N	0.131	neutral	N	0.458510565	None	None	N
E/F	0.7971	likely_pathogenic	0.8337	pathogenic	0.158	Stabilizing	0.993	D	0.725	prob.delet.	None	None	None	None	N
E/G	0.1069	likely_benign	0.1137	benign	-0.633	Destabilizing	0.014	N	0.333	neutral	N	0.514750637	None	None	N
E/H	0.4553	ambiguous	0.4869	ambiguous	0.36	Stabilizing	0.978	D	0.603	neutral	None	None	None	None	N
E/I	0.4797	ambiguous	0.5232	ambiguous	0.389	Stabilizing	0.978	D	0.731	prob.delet.	None	None	None	None	N
E/K	0.221	likely_benign	0.2057	benign	0.136	Stabilizing	0.822	D	0.565	neutral	N	0.433497478	None	None	N
E/L	0.4085	ambiguous	0.4585	ambiguous	0.389	Stabilizing	0.978	D	0.693	prob.neutral	None	None	None	None	N
E/M	0.479	ambiguous	0.5258	ambiguous	0.363	Stabilizing	0.998	D	0.715	prob.delet.	None	None	None	None	N
E/N	0.192	likely_benign	0.219	benign	-0.461	Destabilizing	0.019	N	0.304	neutral	None	None	None	None	N
E/P	0.5916	likely_pathogenic	0.645	pathogenic	0.165	Stabilizing	0.978	D	0.69	prob.neutral	None	None	None	None	N
E/Q	0.133	likely_benign	0.1339	benign	-0.356	Destabilizing	0.942	D	0.599	neutral	N	0.492449781	None	None	N
E/R	0.3352	likely_benign	0.3174	benign	0.501	Stabilizing	0.956	D	0.615	neutral	None	None	None	None	N
E/S	0.1499	likely_benign	0.1694	benign	-0.618	Destabilizing	0.754	D	0.558	neutral	None	None	None	None	N
E/T	0.1975	likely_benign	0.2205	benign	-0.376	Destabilizing	0.86	D	0.633	neutral	None	None	None	None	N
E/V	0.2749	likely_benign	0.3016	benign	0.165	Stabilizing	0.97	D	0.692	prob.neutral	N	0.517809585	None	None	N
E/W	0.8978	likely_pathogenic	0.9159	pathogenic	0.397	Stabilizing	0.998	D	0.755	deleterious	None	None	None	None	N
E/Y	0.6385	likely_pathogenic	0.6836	pathogenic	0.429	Stabilizing	0.993	D	0.726	prob.delet.	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.