TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26244	78955;78956;78957	chr2:178567402;178567401;178567400	chr2:179432129;179432128;179432127
N2AB	24603	74032;74033;74034	chr2:178567402;178567401;178567400	chr2:179432129;179432128;179432127
N2A	23676	71251;71252;71253	chr2:178567402;178567401;178567400	chr2:179432129;179432128;179432127
N2B	17179	51760;51761;51762	chr2:178567402;178567401;178567400	chr2:179432129;179432128;179432127
Novex-1	17304	52135;52136;52137	chr2:178567402;178567401;178567400	chr2:179432129;179432128;179432127
Novex-2	17371	52336;52337;52338	chr2:178567402;178567401;178567400	chr2:179432129;179432128;179432127
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: Ig-137
• Domain position: 52
• Structural Position: 127
• Q(SASA): 0.5772
• 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/D	None	None	0.014	N	0.299	0.264	0.253726318573	gnomAD-4.0.0	6.89519E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.03174E-07	0	0
N/H	None	None	0.97	N	0.59	0.44	0.383921772103	gnomAD-4.0.0	6.89519E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.19383E-05	0
N/S	None	None	0.489	N	0.453	0.181	0.245660935333	gnomAD-4.0.0	3.24203E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.89754E-06	0	3.07711E-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
N/A	0.4112	ambiguous	0.4393	ambiguous	-0.635	Destabilizing	0.754	D	0.593	neutral	None	None	None	None	N
N/C	0.3847	ambiguous	0.4064	ambiguous	0.242	Stabilizing	0.998	D	0.716	prob.delet.	None	None	None	None	N
N/D	0.2459	likely_benign	0.2598	benign	0.084	Stabilizing	0.014	N	0.299	neutral	N	0.517282015	None	None	N
N/E	0.5689	likely_pathogenic	0.6066	pathogenic	0.124	Stabilizing	0.754	D	0.443	neutral	None	None	None	None	N
N/F	0.6909	likely_pathogenic	0.7066	pathogenic	-0.66	Destabilizing	0.978	D	0.705	prob.neutral	None	None	None	None	N
N/G	0.5013	ambiguous	0.5289	ambiguous	-0.913	Destabilizing	0.86	D	0.439	neutral	None	None	None	None	N
N/H	0.1781	likely_benign	0.1894	benign	-0.769	Destabilizing	0.97	D	0.59	neutral	N	0.487138042	None	None	N
N/I	0.2949	likely_benign	0.3028	benign	0.039	Stabilizing	0.942	D	0.707	prob.neutral	N	0.489264409	None	None	N
N/K	0.4677	ambiguous	0.5008	ambiguous	0.027	Stabilizing	0.014	N	0.294	neutral	N	0.51068133	None	None	N
N/L	0.3496	ambiguous	0.3574	ambiguous	0.039	Stabilizing	0.754	D	0.636	neutral	None	None	None	None	N
N/M	0.3689	ambiguous	0.3784	ambiguous	0.42	Stabilizing	0.998	D	0.689	prob.neutral	None	None	None	None	N
N/P	0.7946	likely_pathogenic	0.8057	pathogenic	-0.156	Destabilizing	0.978	D	0.687	prob.neutral	None	None	None	None	N
N/Q	0.48	ambiguous	0.5088	ambiguous	-0.489	Destabilizing	0.956	D	0.567	neutral	None	None	None	None	N
N/R	0.5321	ambiguous	0.5755	pathogenic	0.006	Stabilizing	0.754	D	0.524	neutral	None	None	None	None	N
N/S	0.143	likely_benign	0.1539	benign	-0.456	Destabilizing	0.489	N	0.453	neutral	N	0.45598284	None	None	N
N/T	0.1545	likely_benign	0.1651	benign	-0.23	Destabilizing	0.058	N	0.294	neutral	N	0.470605576	None	None	N
N/V	0.309	likely_benign	0.3167	benign	-0.156	Destabilizing	0.915	D	0.645	neutral	None	None	None	None	N
N/W	0.8458	likely_pathogenic	0.849	pathogenic	-0.492	Destabilizing	0.998	D	0.718	prob.delet.	None	None	None	None	N
N/Y	0.1886	likely_benign	0.1997	benign	-0.267	Destabilizing	0.99	D	0.692	prob.neutral	N	0.518743453	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.