TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20748	62467;62468;62469	chr2:178589483;178589482;178589481	chr2:179454210;179454209;179454208
N2AB	19107	57544;57545;57546	chr2:178589483;178589482;178589481	chr2:179454210;179454209;179454208
N2A	18180	54763;54764;54765	chr2:178589483;178589482;178589481	chr2:179454210;179454209;179454208
N2B	11683	35272;35273;35274	chr2:178589483;178589482;178589481	chr2:179454210;179454209;179454208
Novex-1	11808	35647;35648;35649	chr2:178589483;178589482;178589481	chr2:179454210;179454209;179454208
Novex-2	11875	35848;35849;35850	chr2:178589483;178589482;178589481	chr2:179454210;179454209;179454208
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-38
• Domain position: 81
• Structural Position: 113
• Q(SASA): 0.6937
• Predicted PPI site: I

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	rs774998817	None	0.978	N	0.537	0.309	0.393775345888	gnomAD-4.0.0	1.5921E-06	None	None	None	None	I	None	0	2.28843E-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
E/A	0.3726	ambiguous	0.3836	ambiguous	-0.176	Destabilizing	0.989	D	0.595	neutral	N	0.463876313	None	None	I
E/C	0.9645	likely_pathogenic	0.9691	pathogenic	0.056	Stabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	I
E/D	0.2267	likely_benign	0.2485	benign	-0.264	Destabilizing	0.121	N	0.316	neutral	N	0.466455258	None	None	I
E/F	0.9402	likely_pathogenic	0.9453	pathogenic	-0.151	Destabilizing	0.995	D	0.659	neutral	None	None	None	None	I
E/G	0.5662	likely_pathogenic	0.5475	ambiguous	-0.327	Destabilizing	0.978	D	0.546	neutral	N	0.511683328	None	None	I
E/H	0.839	likely_pathogenic	0.8477	pathogenic	0.202	Stabilizing	1.0	D	0.461	neutral	None	None	None	None	I
E/I	0.5941	likely_pathogenic	0.6278	pathogenic	0.173	Stabilizing	0.99	D	0.645	neutral	None	None	None	None	I
E/K	0.4556	ambiguous	0.4802	ambiguous	0.585	Stabilizing	0.978	D	0.537	neutral	N	0.475709459	None	None	I
E/L	0.728	likely_pathogenic	0.7591	pathogenic	0.173	Stabilizing	0.296	N	0.543	neutral	None	None	None	None	I
E/M	0.755	likely_pathogenic	0.7719	pathogenic	0.175	Stabilizing	0.999	D	0.629	neutral	None	None	None	None	I
E/N	0.6092	likely_pathogenic	0.6327	pathogenic	0.237	Stabilizing	0.995	D	0.477	neutral	None	None	None	None	I
E/P	0.8369	likely_pathogenic	0.8504	pathogenic	0.076	Stabilizing	0.999	D	0.553	neutral	None	None	None	None	I
E/Q	0.3813	ambiguous	0.3955	ambiguous	0.269	Stabilizing	0.997	D	0.461	neutral	N	0.509187315	None	None	I
E/R	0.6307	likely_pathogenic	0.6356	pathogenic	0.712	Stabilizing	0.998	D	0.481	neutral	None	None	None	None	I
E/S	0.5302	ambiguous	0.534	ambiguous	0.129	Stabilizing	0.983	D	0.519	neutral	None	None	None	None	I
E/T	0.5416	ambiguous	0.5501	ambiguous	0.264	Stabilizing	0.998	D	0.511	neutral	None	None	None	None	I
E/V	0.4425	ambiguous	0.471	ambiguous	0.076	Stabilizing	0.956	D	0.55	neutral	N	0.512766338	None	None	I
E/W	0.9798	likely_pathogenic	0.9812	pathogenic	-0.051	Destabilizing	1.0	D	0.734	prob.delet.	None	None	None	None	I
E/Y	0.8952	likely_pathogenic	0.9006	pathogenic	0.089	Stabilizing	0.999	D	0.639	neutral	None	None	None	None	I

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.