TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9748	29467;29468;29469	chr2:178706632;178706631;178706630	chr2:179571359;179571358;179571357
N2AB	9431	28516;28517;28518	chr2:178706632;178706631;178706630	chr2:179571359;179571358;179571357
N2A	8504	25735;25736;25737	chr2:178706632;178706631;178706630	chr2:179571359;179571358;179571357
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAC
• RefSeq wild type template codon: GTG
• Domain: Ig-83
• Domain position: 51
• Structural Position: 125
• Q(SASA): 0.6299
• 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
H/N	None	None	0.049	None	0.181	0.097	0.218845423259	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
H/A	0.3705	ambiguous	0.2739	benign	0.458	Stabilizing	0.015	N	0.243	neutral	None	None	None	None	N
H/C	0.2626	likely_benign	0.173	benign	0.905	Stabilizing	0.781	D	0.373	neutral	None	None	None	None	N
H/D	0.3736	ambiguous	0.255	benign	0.016	Stabilizing	None	N	0.089	neutral	None	None	None	None	N
H/E	0.3115	likely_benign	0.2406	benign	0.046	Stabilizing	None	N	0.054	neutral	None	None	None	None	N
H/F	0.2931	likely_benign	0.2206	benign	1.171	Stabilizing	0.076	N	0.367	neutral	None	None	None	None	N
H/G	0.542	ambiguous	0.3746	ambiguous	0.166	Stabilizing	0.064	N	0.287	neutral	None	None	None	None	N
H/I	0.254	likely_benign	0.211	benign	1.204	Stabilizing	0.033	N	0.396	neutral	None	None	None	None	N
H/K	0.2599	likely_benign	0.2276	benign	0.37	Stabilizing	0.015	N	0.219	neutral	None	None	None	None	N
H/L	0.1282	likely_benign	0.0999	benign	1.204	Stabilizing	None	N	0.144	neutral	None	None	None	None	N
H/M	0.4638	ambiguous	0.3933	ambiguous	0.898	Stabilizing	0.367	N	0.42	neutral	None	None	None	None	N
H/N	0.1426	likely_benign	0.1133	benign	0.384	Stabilizing	0.049	N	0.181	neutral	None	None	None	None	N
H/P	0.86	likely_pathogenic	0.5812	pathogenic	0.981	Stabilizing	0.202	N	0.426	neutral	None	None	None	None	N
H/Q	0.1574	likely_benign	0.1224	benign	0.504	Stabilizing	None	N	0.054	neutral	None	None	None	None	N
H/R	0.1218	likely_benign	0.1015	benign	-0.321	Destabilizing	0.025	N	0.171	neutral	None	None	None	None	N
H/S	0.2478	likely_benign	0.1775	benign	0.543	Stabilizing	0.015	N	0.243	neutral	None	None	None	None	N
H/T	0.2622	likely_benign	0.2078	benign	0.67	Stabilizing	0.064	N	0.282	neutral	None	None	None	None	N
H/V	0.235	likely_benign	0.1855	benign	0.981	Stabilizing	0.033	N	0.332	neutral	None	None	None	None	N
H/W	0.418	ambiguous	0.3027	benign	1.148	Stabilizing	0.54	D	0.363	neutral	None	None	None	None	N
H/Y	0.1074	likely_benign	0.075	benign	1.42	Stabilizing	None	N	0.091	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.