TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30444	91555;91556;91557	chr2:178551201;178551200;178551199	chr2:179415928;179415927;179415926
N2AB	28803	86632;86633;86634	chr2:178551201;178551200;178551199	chr2:179415928;179415927;179415926
N2A	27876	83851;83852;83853	chr2:178551201;178551200;178551199	chr2:179415928;179415927;179415926
N2B	21379	64360;64361;64362	chr2:178551201;178551200;178551199	chr2:179415928;179415927;179415926
Novex-1	21504	64735;64736;64737	chr2:178551201;178551200;178551199	chr2:179415928;179415927;179415926
Novex-2	21571	64936;64937;64938	chr2:178551201;178551200;178551199	chr2:179415928;179415927;179415926
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: Fn3-110
• Domain position: 23
• Structural Position: 25
• Q(SASA): 0.3584
• 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	None	None	0.801	N	0.396	0.107	0.0806252709748	gnomAD-4.0.0	6.84333E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99572E-07	0	0
N/S	None	None	0.454	N	0.395	0.174	0.110078149338	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
N/A	0.2162	likely_benign	0.1996	benign	-0.598	Destabilizing	0.525	D	0.433	neutral	None	None	None	None	N
N/C	0.3146	likely_benign	0.2958	benign	0.248	Stabilizing	0.998	D	0.587	neutral	None	None	None	None	N
N/D	0.1805	likely_benign	0.1831	benign	-0.094	Destabilizing	0.005	N	0.12	neutral	N	0.407310954	None	None	N
N/E	0.3179	likely_benign	0.3223	benign	-0.056	Destabilizing	0.029	N	0.141	neutral	None	None	None	None	N
N/F	0.4972	ambiguous	0.4786	ambiguous	-0.577	Destabilizing	0.974	D	0.592	neutral	None	None	None	None	N
N/G	0.3472	ambiguous	0.3237	benign	-0.879	Destabilizing	0.688	D	0.389	neutral	None	None	None	None	N
N/H	0.1267	likely_benign	0.1273	benign	-0.804	Destabilizing	0.989	D	0.479	neutral	N	0.483483581	None	None	N
N/I	0.1801	likely_benign	0.1868	benign	0.086	Stabilizing	0.934	D	0.598	neutral	N	0.447216136	None	None	N
N/K	0.2818	likely_benign	0.294	benign	-0.204	Destabilizing	0.801	D	0.396	neutral	N	0.40007555	None	None	N
N/L	0.1987	likely_benign	0.1959	benign	0.086	Stabilizing	0.728	D	0.561	neutral	None	None	None	None	N
N/M	0.2537	likely_benign	0.2544	benign	0.431	Stabilizing	0.998	D	0.552	neutral	None	None	None	None	N
N/P	0.7495	likely_pathogenic	0.714	pathogenic	-0.113	Destabilizing	0.974	D	0.619	neutral	None	None	None	None	N
N/Q	0.2652	likely_benign	0.2572	benign	-0.587	Destabilizing	0.842	D	0.455	neutral	None	None	None	None	N
N/R	0.3577	ambiguous	0.3591	ambiguous	-0.251	Destabilizing	0.842	D	0.454	neutral	None	None	None	None	N
N/S	0.1042	likely_benign	0.1	benign	-0.53	Destabilizing	0.454	N	0.395	neutral	N	0.366520337	None	None	N
N/T	0.1161	likely_benign	0.1134	benign	-0.318	Destabilizing	0.051	N	0.157	neutral	N	0.371619513	None	None	N
N/V	0.1908	likely_benign	0.1932	benign	-0.113	Destabilizing	0.728	D	0.563	neutral	None	None	None	None	N
N/W	0.7612	likely_pathogenic	0.7546	pathogenic	-0.454	Destabilizing	0.998	D	0.648	neutral	None	None	None	None	N
N/Y	0.1699	likely_benign	0.1668	benign	-0.245	Destabilizing	0.989	D	0.587	neutral	N	0.467495408	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.