TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21626	65101;65102;65103	chr2:178584765;178584764;178584763	chr2:179449492;179449491;179449490
N2AB	19985	60178;60179;60180	chr2:178584765;178584764;178584763	chr2:179449492;179449491;179449490
N2A	19058	57397;57398;57399	chr2:178584765;178584764;178584763	chr2:179449492;179449491;179449490
N2B	12561	37906;37907;37908	chr2:178584765;178584764;178584763	chr2:179449492;179449491;179449490
Novex-1	12686	38281;38282;38283	chr2:178584765;178584764;178584763	chr2:179449492;179449491;179449490
Novex-2	12753	38482;38483;38484	chr2:178584765;178584764;178584763	chr2:179449492;179449491;179449490
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-44
• Domain position: 68
• Structural Position: 99
• Q(SASA): 0.5494
• 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
P/L	None	None	0.961	N	0.547	0.514	0.611689863146	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05
P/T	rs2048562251	None	0.248	N	0.262	0.327	0.335661160332	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.07125E-04	0
P/T	rs2048562251	None	0.248	N	0.262	0.327	0.335661160332	gnomAD-4.0.0	6.57739E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.07125E-04	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
P/A	0.0835	likely_benign	0.0872	benign	-0.887	Destabilizing	0.248	N	0.262	neutral	N	0.483793452	None	None	N
P/C	0.5228	ambiguous	0.5306	ambiguous	-0.67	Destabilizing	0.351	N	0.433	neutral	None	None	None	None	N
P/D	0.6223	likely_pathogenic	0.6988	pathogenic	-0.743	Destabilizing	0.996	D	0.413	neutral	None	None	None	None	N
P/E	0.3371	likely_benign	0.3941	ambiguous	-0.841	Destabilizing	0.996	D	0.416	neutral	None	None	None	None	N
P/F	0.6601	likely_pathogenic	0.6963	pathogenic	-0.978	Destabilizing	0.999	D	0.624	neutral	None	None	None	None	N
P/G	0.3784	ambiguous	0.3984	ambiguous	-1.075	Destabilizing	0.97	D	0.468	neutral	None	None	None	None	N
P/H	0.2405	likely_benign	0.2937	benign	-0.596	Destabilizing	1.0	D	0.535	neutral	None	None	None	None	N
P/I	0.387	ambiguous	0.4111	ambiguous	-0.522	Destabilizing	0.991	D	0.596	neutral	None	None	None	None	N
P/K	0.2977	likely_benign	0.3624	ambiguous	-0.764	Destabilizing	0.996	D	0.422	neutral	None	None	None	None	N
P/L	0.1611	likely_benign	0.1862	benign	-0.522	Destabilizing	0.961	D	0.547	neutral	N	0.496977091	None	None	N
P/M	0.3899	ambiguous	0.415	ambiguous	-0.372	Destabilizing	1.0	D	0.54	neutral	None	None	None	None	N
P/N	0.4587	ambiguous	0.5027	ambiguous	-0.449	Destabilizing	0.996	D	0.519	neutral	None	None	None	None	N
P/Q	0.1821	likely_benign	0.212	benign	-0.728	Destabilizing	0.998	D	0.43	neutral	D	0.530982031	None	None	N
P/R	0.1705	likely_benign	0.2275	benign	-0.149	Destabilizing	0.994	D	0.529	neutral	D	0.532136824	None	None	N
P/S	0.1588	likely_benign	0.1752	benign	-0.839	Destabilizing	0.925	D	0.401	neutral	N	0.486581837	None	None	N
P/T	0.1046	likely_benign	0.1127	benign	-0.838	Destabilizing	0.248	N	0.262	neutral	N	0.507643812	None	None	N
P/V	0.2507	likely_benign	0.2692	benign	-0.607	Destabilizing	0.97	D	0.466	neutral	None	None	None	None	N
P/W	0.7467	likely_pathogenic	0.8042	pathogenic	-1.056	Destabilizing	1.0	D	0.657	neutral	None	None	None	None	N
P/Y	0.5719	likely_pathogenic	0.6229	pathogenic	-0.777	Destabilizing	0.999	D	0.623	neutral	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.