TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31317	94174;94175;94176	chr2:178547677;178547676;178547675	chr2:179412404;179412403;179412402
N2AB	29676	89251;89252;89253	chr2:178547677;178547676;178547675	chr2:179412404;179412403;179412402
N2A	28749	86470;86471;86472	chr2:178547677;178547676;178547675	chr2:179412404;179412403;179412402
N2B	22252	66979;66980;66981	chr2:178547677;178547676;178547675	chr2:179412404;179412403;179412402
Novex-1	22377	67354;67355;67356	chr2:178547677;178547676;178547675	chr2:179412404;179412403;179412402
Novex-2	22444	67555;67556;67557	chr2:178547677;178547676;178547675	chr2:179412404;179412403;179412402
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-116
• Domain position: 10
• Structural Position: 11
• Q(SASA): 0.611
• 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
E/K	None	None	0.008	N	0.338	0.115	0.197625483188	gnomAD-4.0.0	1.59105E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85786E-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
E/A	0.1162	likely_benign	0.1274	benign	-0.39	Destabilizing	0.565	D	0.614	neutral	N	0.466671523	None	None	N
E/C	0.6234	likely_pathogenic	0.6798	pathogenic	-0.024	Destabilizing	0.996	D	0.774	deleterious	None	None	None	None	N
E/D	0.1146	likely_benign	0.1119	benign	-0.418	Destabilizing	0.003	N	0.169	neutral	N	0.514113132	None	None	N
E/F	0.5698	likely_pathogenic	0.6166	pathogenic	-0.222	Destabilizing	0.987	D	0.765	deleterious	None	None	None	None	N
E/G	0.1852	likely_benign	0.2236	benign	-0.599	Destabilizing	0.722	D	0.627	neutral	N	0.478788297	None	None	N
E/H	0.2471	likely_benign	0.2675	benign	-0.029	Destabilizing	0.989	D	0.583	neutral	None	None	None	None	N
E/I	0.1862	likely_benign	0.196	benign	0.13	Stabilizing	0.961	D	0.775	deleterious	None	None	None	None	N
E/K	0.0932	likely_benign	0.1178	benign	0.402	Stabilizing	0.008	N	0.338	neutral	N	0.475861388	None	None	N
E/L	0.2203	likely_benign	0.2478	benign	0.13	Stabilizing	0.923	D	0.715	prob.delet.	None	None	None	None	N
E/M	0.272	likely_benign	0.3035	benign	0.229	Stabilizing	0.996	D	0.745	deleterious	None	None	None	None	N
E/N	0.1651	likely_benign	0.172	benign	-0.016	Destabilizing	0.633	D	0.572	neutral	None	None	None	None	N
E/P	0.8204	likely_pathogenic	0.8243	pathogenic	-0.023	Destabilizing	0.961	D	0.707	prob.neutral	None	None	None	None	N
E/Q	0.1006	likely_benign	0.1091	benign	0.03	Stabilizing	0.722	D	0.565	neutral	N	0.488753328	None	None	N
E/R	0.1579	likely_benign	0.188	benign	0.58	Stabilizing	0.858	D	0.577	neutral	None	None	None	None	N
E/S	0.1399	likely_benign	0.1471	benign	-0.147	Destabilizing	0.775	D	0.539	neutral	None	None	None	None	N
E/T	0.1292	likely_benign	0.1303	benign	0.03	Stabilizing	0.923	D	0.667	neutral	None	None	None	None	N
E/V	0.1169	likely_benign	0.1182	benign	-0.023	Destabilizing	0.901	D	0.685	prob.neutral	N	0.494103219	None	None	N
E/W	0.7833	likely_pathogenic	0.8306	pathogenic	-0.048	Destabilizing	0.996	D	0.755	deleterious	None	None	None	None	N
E/Y	0.4357	ambiguous	0.4659	ambiguous	0.035	Stabilizing	0.987	D	0.757	deleterious	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.