TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34178	102757;102758;102759	chr2:178534083;178534082;178534081	chr2:179398810;179398809;179398808
N2AB	32537	97834;97835;97836	chr2:178534083;178534082;178534081	chr2:179398810;179398809;179398808
N2A	31610	95053;95054;95055	chr2:178534083;178534082;178534081	chr2:179398810;179398809;179398808
N2B	25113	75562;75563;75564	chr2:178534083;178534082;178534081	chr2:179398810;179398809;179398808
Novex-1	25238	75937;75938;75939	chr2:178534083;178534082;178534081	chr2:179398810;179398809;179398808
Novex-2	25305	76138;76139;76140	chr2:178534083;178534082;178534081	chr2:179398810;179398809;179398808
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-160
• Domain position: 42
• Structural Position: 59
• Q(SASA): 0.4266
• 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	rs774700628	0.331	0.99	N	0.468	0.193	0.281780670237	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.87E-06	0
E/Q	rs774700628	0.331	0.99	N	0.468	0.193	0.281780670237	gnomAD-4.0.0	2.73664E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.59766E-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	0.2591	likely_benign	0.2405	benign	-0.074	Destabilizing	0.99	D	0.555	neutral	N	0.478878343	None	None	N
E/C	0.9186	likely_pathogenic	0.9148	pathogenic	-0.258	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
E/D	0.2262	likely_benign	0.232	benign	-0.326	Destabilizing	0.977	D	0.489	neutral	N	0.474896675	None	None	N
E/F	0.8774	likely_pathogenic	0.8732	pathogenic	0.043	Stabilizing	0.998	D	0.623	neutral	None	None	None	None	N
E/G	0.2458	likely_benign	0.227	benign	-0.229	Destabilizing	0.99	D	0.535	neutral	N	0.48978877	None	None	N
E/H	0.6117	likely_pathogenic	0.5676	pathogenic	0.632	Stabilizing	0.171	N	0.201	neutral	None	None	None	None	N
E/I	0.5628	ambiguous	0.545	ambiguous	0.285	Stabilizing	0.999	D	0.618	neutral	None	None	None	None	N
E/K	0.198	likely_benign	0.1734	benign	0.418	Stabilizing	0.99	D	0.539	neutral	N	0.454134614	None	None	N
E/L	0.5765	likely_pathogenic	0.5516	ambiguous	0.285	Stabilizing	0.998	D	0.538	neutral	None	None	None	None	N
E/M	0.6455	likely_pathogenic	0.6255	pathogenic	0.034	Stabilizing	1.0	D	0.589	neutral	None	None	None	None	N
E/N	0.4063	ambiguous	0.4065	ambiguous	0.005	Stabilizing	0.985	D	0.508	neutral	None	None	None	None	N
E/P	0.7222	likely_pathogenic	0.6948	pathogenic	0.185	Stabilizing	0.999	D	0.531	neutral	None	None	None	None	N
E/Q	0.1736	likely_benign	0.1525	benign	0.055	Stabilizing	0.99	D	0.468	neutral	N	0.464775682	None	None	N
E/R	0.3266	likely_benign	0.2778	benign	0.717	Stabilizing	0.985	D	0.472	neutral	None	None	None	None	N
E/S	0.3007	likely_benign	0.2893	benign	-0.111	Destabilizing	0.993	D	0.5	neutral	None	None	None	None	N
E/T	0.3302	likely_benign	0.3186	benign	0.03	Stabilizing	0.999	D	0.495	neutral	None	None	None	None	N
E/V	0.3393	likely_benign	0.3183	benign	0.185	Stabilizing	0.999	D	0.508	neutral	N	0.486191104	None	None	N
E/W	0.9486	likely_pathogenic	0.9425	pathogenic	0.144	Stabilizing	1.0	D	0.68	prob.neutral	None	None	None	None	N
E/Y	0.7995	likely_pathogenic	0.7898	pathogenic	0.281	Stabilizing	0.996	D	0.52	neutral	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.