TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25654	77185;77186;77187	chr2:178569172;178569171;178569170	chr2:179433899;179433898;179433897
N2AB	24013	72262;72263;72264	chr2:178569172;178569171;178569170	chr2:179433899;179433898;179433897
N2A	23086	69481;69482;69483	chr2:178569172;178569171;178569170	chr2:179433899;179433898;179433897
N2B	16589	49990;49991;49992	chr2:178569172;178569171;178569170	chr2:179433899;179433898;179433897
Novex-1	16714	50365;50366;50367	chr2:178569172;178569171;178569170	chr2:179433899;179433898;179433897
Novex-2	16781	50566;50567;50568	chr2:178569172;178569171;178569170	chr2:179433899;179433898;179433897
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Fn3-74
• Domain position: 54
• Structural Position: 75
• Q(SASA): 0.5751
• 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
N/K	rs755800765	0.231	0.005	N	0.152	0.147	0.0297737177859	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	8.72E-05	None	0	0	None	0	None	0	0	0
N/K	rs755800765	0.231	0.005	N	0.152	0.147	0.0297737177859	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	6.56E-05	0	0	0	None	0	0	0	0	0
N/K	rs755800765	0.231	0.005	N	0.152	0.147	0.0297737177859	gnomAD-4.0.0	6.41134E-06	None	None	None	None	N	None	0	8.4832E-05	None	0	0	None	0	0	0	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
N/A	0.1864	likely_benign	0.2482	benign	-0.589	Destabilizing	0.012	N	0.369	neutral	None	None	None	None	N
N/C	0.2935	likely_benign	0.3564	ambiguous	0.401	Stabilizing	0.98	D	0.39	neutral	None	None	None	None	N
N/D	0.1978	likely_benign	0.2502	benign	-0.173	Destabilizing	0.116	N	0.349	neutral	N	0.50362678	None	None	N
N/E	0.525	ambiguous	0.6232	pathogenic	-0.157	Destabilizing	0.225	N	0.313	neutral	None	None	None	None	N
N/F	0.5887	likely_pathogenic	0.6902	pathogenic	-0.67	Destabilizing	0.979	D	0.385	neutral	None	None	None	None	N
N/G	0.227	likely_benign	0.2969	benign	-0.847	Destabilizing	0.376	N	0.315	neutral	None	None	None	None	N
N/H	0.146	likely_benign	0.1732	benign	-0.857	Destabilizing	0.813	D	0.392	neutral	N	0.468584081	None	None	N
N/I	0.317	likely_benign	0.3915	ambiguous	0.03	Stabilizing	0.682	D	0.409	neutral	N	0.479923479	None	None	N
N/K	0.457	ambiguous	0.5446	ambiguous	-0.17	Destabilizing	0.005	N	0.152	neutral	N	0.450909802	None	None	N
N/L	0.2924	likely_benign	0.358	ambiguous	0.03	Stabilizing	0.448	N	0.38	neutral	None	None	None	None	N
N/M	0.3915	ambiguous	0.4696	ambiguous	0.516	Stabilizing	0.985	D	0.367	neutral	None	None	None	None	N
N/P	0.7881	likely_pathogenic	0.8264	pathogenic	-0.148	Destabilizing	0.553	D	0.378	neutral	None	None	None	None	N
N/Q	0.3981	ambiguous	0.4768	ambiguous	-0.53	Destabilizing	0.74	D	0.35	neutral	None	None	None	None	N
N/R	0.4753	ambiguous	0.5695	pathogenic	-0.175	Destabilizing	0.521	D	0.349	neutral	None	None	None	None	N
N/S	0.0781	likely_benign	0.0865	benign	-0.399	Destabilizing	0.027	N	0.381	neutral	N	0.48683053	None	None	N
N/T	0.138	likely_benign	0.1664	benign	-0.222	Destabilizing	0.001	N	0.105	neutral	N	0.455968905	None	None	N
N/V	0.2522	likely_benign	0.3142	benign	-0.148	Destabilizing	0.064	N	0.407	neutral	None	None	None	None	N
N/W	0.8505	likely_pathogenic	0.8925	pathogenic	-0.577	Destabilizing	0.994	D	0.547	neutral	None	None	None	None	N
N/Y	0.2419	likely_benign	0.296	benign	-0.368	Destabilizing	0.973	D	0.371	neutral	N	0.46776116	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.