TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30294	91105;91106;91107	chr2:178552020;178552019;178552018	chr2:179416747;179416746;179416745
N2AB	28653	86182;86183;86184	chr2:178552020;178552019;178552018	chr2:179416747;179416746;179416745
N2A	27726	83401;83402;83403	chr2:178552020;178552019;178552018	chr2:179416747;179416746;179416745
N2B	21229	63910;63911;63912	chr2:178552020;178552019;178552018	chr2:179416747;179416746;179416745
Novex-1	21354	64285;64286;64287	chr2:178552020;178552019;178552018	chr2:179416747;179416746;179416745
Novex-2	21421	64486;64487;64488	chr2:178552020;178552019;178552018	chr2:179416747;179416746;179416745
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: Fn3-108
• Domain position: 71
• Structural Position: 103
• Q(SASA): 0.3784
• 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	None	None	0.989	N	0.573	0.559	0.469333501611	gnomAD-4.0.0	1.59281E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86157E-06	0	0
E/D	None	None	0.989	N	0.43	0.219	0.240491677333	gnomAD-4.0.0	2.05356E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69941E-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
E/A	0.2061	likely_benign	0.1762	benign	-0.918	Destabilizing	0.989	D	0.573	neutral	N	0.490348867	None	None	N
E/C	0.8958	likely_pathogenic	0.897	pathogenic	-0.43	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
E/D	0.3177	likely_benign	0.2966	benign	-0.925	Destabilizing	0.989	D	0.43	neutral	N	0.468116782	None	None	N
E/F	0.8945	likely_pathogenic	0.8834	pathogenic	-0.143	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	N
E/G	0.3621	ambiguous	0.3063	benign	-1.299	Destabilizing	0.998	D	0.717	prob.delet.	N	0.48929891	None	None	N
E/H	0.7195	likely_pathogenic	0.6722	pathogenic	-0.291	Destabilizing	1.0	D	0.734	prob.delet.	None	None	None	None	N
E/I	0.4804	ambiguous	0.4702	ambiguous	0.131	Stabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
E/K	0.2871	likely_benign	0.2226	benign	-0.355	Destabilizing	0.978	D	0.48	neutral	N	0.478939655	None	None	N
E/L	0.5675	likely_pathogenic	0.5229	ambiguous	0.131	Stabilizing	0.998	D	0.74	deleterious	None	None	None	None	N
E/M	0.6017	likely_pathogenic	0.5723	pathogenic	0.533	Stabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
E/N	0.4816	ambiguous	0.4366	ambiguous	-0.973	Destabilizing	0.999	D	0.705	prob.neutral	None	None	None	None	N
E/P	0.5661	likely_pathogenic	0.5302	ambiguous	-0.198	Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
E/Q	0.1854	likely_benign	0.1629	benign	-0.831	Destabilizing	0.775	D	0.299	neutral	N	0.503762852	None	None	N
E/R	0.4755	ambiguous	0.4002	ambiguous	-0.032	Destabilizing	0.998	D	0.689	prob.neutral	None	None	None	None	N
E/S	0.3152	likely_benign	0.2696	benign	-1.302	Destabilizing	0.992	D	0.535	neutral	None	None	None	None	N
E/T	0.3264	likely_benign	0.2977	benign	-0.971	Destabilizing	0.999	D	0.755	deleterious	None	None	None	None	N
E/V	0.2951	likely_benign	0.2844	benign	-0.198	Destabilizing	0.998	D	0.761	deleterious	N	0.484450291	None	None	N
E/W	0.9741	likely_pathogenic	0.97	pathogenic	0.227	Stabilizing	1.0	D	0.758	deleterious	None	None	None	None	N
E/Y	0.8383	likely_pathogenic	0.8136	pathogenic	0.166	Stabilizing	1.0	D	0.79	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.