TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26832	80719;80720;80721	chr2:178565638;178565637;178565636	chr2:179430365;179430364;179430363
N2AB	25191	75796;75797;75798	chr2:178565638;178565637;178565636	chr2:179430365;179430364;179430363
N2A	24264	73015;73016;73017	chr2:178565638;178565637;178565636	chr2:179430365;179430364;179430363
N2B	17767	53524;53525;53526	chr2:178565638;178565637;178565636	chr2:179430365;179430364;179430363
Novex-1	17892	53899;53900;53901	chr2:178565638;178565637;178565636	chr2:179430365;179430364;179430363
Novex-2	17959	54100;54101;54102	chr2:178565638;178565637;178565636	chr2:179430365;179430364;179430363
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: Fn3-83
• Domain position: 53
• Structural Position: 70
• Q(SASA): 0.7798
• 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	rs780512337	0.932	0.669	N	0.433	0.254	0.243398259712	gnomAD-2.1.1	1.21E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	2.67E-05	0
E/K	rs780512337	0.932	0.669	N	0.433	0.254	0.243398259712	gnomAD-4.0.0	4.77482E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.57741E-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	0.18	likely_benign	0.1687	benign	-0.421	Destabilizing	0.625	D	0.478	neutral	N	0.504837501	None	None	I
E/C	0.8354	likely_pathogenic	0.8296	pathogenic	-0.138	Destabilizing	0.998	D	0.463	neutral	None	None	None	None	I
E/D	0.1451	likely_benign	0.1392	benign	-0.426	Destabilizing	0.012	N	0.184	neutral	N	0.465108464	None	None	I
E/F	0.7018	likely_pathogenic	0.6877	pathogenic	-0.039	Destabilizing	0.974	D	0.489	neutral	None	None	None	None	I
E/G	0.2534	likely_benign	0.2242	benign	-0.671	Destabilizing	0.801	D	0.509	neutral	N	0.466355582	None	None	I
E/H	0.3942	ambiguous	0.4052	ambiguous	0.151	Stabilizing	0.974	D	0.509	neutral	None	None	None	None	I
E/I	0.2977	likely_benign	0.2835	benign	0.221	Stabilizing	0.728	D	0.523	neutral	None	None	None	None	I
E/K	0.1583	likely_benign	0.1474	benign	0.345	Stabilizing	0.669	D	0.433	neutral	N	0.508283238	None	None	I
E/L	0.3804	ambiguous	0.3691	ambiguous	0.221	Stabilizing	0.728	D	0.499	neutral	None	None	None	None	I
E/M	0.436	ambiguous	0.4206	ambiguous	0.283	Stabilizing	0.974	D	0.482	neutral	None	None	None	None	I
E/N	0.2229	likely_benign	0.2152	benign	-0.215	Destabilizing	0.728	D	0.46	neutral	None	None	None	None	I
E/P	0.6801	likely_pathogenic	0.6452	pathogenic	0.028	Stabilizing	0.974	D	0.531	neutral	None	None	None	None	I
E/Q	0.1271	likely_benign	0.1302	benign	-0.127	Destabilizing	0.136	N	0.24	neutral	D	0.524252768	None	None	I
E/R	0.2662	likely_benign	0.2715	benign	0.6	Stabilizing	0.842	D	0.5	neutral	None	None	None	None	I
E/S	0.1839	likely_benign	0.1783	benign	-0.358	Destabilizing	0.525	D	0.441	neutral	None	None	None	None	I
E/T	0.1621	likely_benign	0.157	benign	-0.14	Destabilizing	0.029	N	0.235	neutral	None	None	None	None	I
E/V	0.1732	likely_benign	0.1678	benign	0.028	Stabilizing	0.051	N	0.376	neutral	N	0.460548095	None	None	I
E/W	0.8938	likely_pathogenic	0.8934	pathogenic	0.198	Stabilizing	0.998	D	0.503	neutral	None	None	None	None	I
E/Y	0.5905	likely_pathogenic	0.5831	pathogenic	0.234	Stabilizing	0.991	D	0.491	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.