TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6964	21115;21116;21117	chr2:178724485;178724484;178724483	chr2:179589212;179589211;179589210
N2AB	6647	20164;20165;20166	chr2:178724485;178724484;178724483	chr2:179589212;179589211;179589210
N2A	5720	17383;17384;17385	chr2:178724485;178724484;178724483	chr2:179589212;179589211;179589210
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: T
• RefSeq wild type transcript codon: ACG
• RefSeq wild type template codon: TGC
• Domain: Ig-54
• Domain position: 17
• Structural Position: 26
• Q(SASA): 0.357
• 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
T/M	rs765257439	0.043	0.086	N	0.285	0.11	0.366848117066	gnomAD-2.1.1	6.86E-05	None	None	None	None	N	None	0	0	None	0	0	None	5.24418E-04	None	0	8.91E-06	0
T/M	rs765257439	0.043	0.086	N	0.285	0.11	0.366848117066	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	1.47E-05	0	0
T/M	rs765257439	0.043	0.086	N	0.285	0.11	0.366848117066	gnomAD-4.0.0	3.41182E-05	None	None	None	None	N	None	1.3364E-05	0	None	0	0	None	0	0	7.63575E-06	4.83729E-04	1.60339E-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
T/A	0.0821	likely_benign	0.0772	benign	-0.882	Destabilizing	0.001	N	0.083	neutral	N	0.49978868	None	None	N
T/C	0.525	ambiguous	0.4735	ambiguous	-0.487	Destabilizing	0.94	D	0.351	neutral	None	None	None	None	N
T/D	0.334	likely_benign	0.2991	benign	-0.075	Destabilizing	0.593	D	0.404	neutral	None	None	None	None	N
T/E	0.3147	likely_benign	0.2814	benign	-0.061	Destabilizing	0.418	N	0.352	neutral	None	None	None	None	N
T/F	0.2506	likely_benign	0.2061	benign	-0.925	Destabilizing	0.716	D	0.426	neutral	None	None	None	None	N
T/G	0.2659	likely_benign	0.2237	benign	-1.156	Destabilizing	0.264	N	0.407	neutral	None	None	None	None	N
T/H	0.2802	likely_benign	0.2453	benign	-1.383	Destabilizing	0.983	D	0.361	neutral	None	None	None	None	N
T/I	0.1579	likely_benign	0.1386	benign	-0.24	Destabilizing	0.002	N	0.234	neutral	None	None	None	None	N
T/K	0.2459	likely_benign	0.2168	benign	-0.639	Destabilizing	0.579	D	0.363	neutral	N	0.493073351	None	None	N
T/L	0.1131	likely_benign	0.1032	benign	-0.24	Destabilizing	0.022	N	0.324	neutral	None	None	None	None	N
T/M	0.0903	likely_benign	0.0821	benign	0.075	Stabilizing	0.086	N	0.285	neutral	N	0.515470208	None	None	N
T/N	0.0966	likely_benign	0.086	benign	-0.605	Destabilizing	0.836	D	0.356	neutral	None	None	None	None	N
T/P	0.088	likely_benign	0.0862	benign	-0.422	Destabilizing	0.001	N	0.179	neutral	N	0.451341372	None	None	N
T/Q	0.2441	likely_benign	0.22	benign	-0.747	Destabilizing	0.836	D	0.409	neutral	None	None	None	None	N
T/R	0.1978	likely_benign	0.1782	benign	-0.438	Destabilizing	0.828	D	0.411	neutral	N	0.492611991	None	None	N
T/S	0.1045	likely_benign	0.0929	benign	-0.946	Destabilizing	0.101	N	0.313	neutral	N	0.460286142	None	None	N
T/V	0.1453	likely_benign	0.1257	benign	-0.422	Destabilizing	0.001	N	0.099	neutral	None	None	None	None	N
T/W	0.6148	likely_pathogenic	0.563	ambiguous	-0.835	Destabilizing	0.983	D	0.406	neutral	None	None	None	None	N
T/Y	0.2555	likely_benign	0.2315	benign	-0.604	Destabilizing	0.836	D	0.394	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.