TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35364	106315;106316;106317	chr2:178530525;178530524;178530523	chr2:179395252;179395251;179395250
N2AB	33723	101392;101393;101394	chr2:178530525;178530524;178530523	chr2:179395252;179395251;179395250
N2A	32796	98611;98612;98613	chr2:178530525;178530524;178530523	chr2:179395252;179395251;179395250
N2B	26299	79120;79121;79122	chr2:178530525;178530524;178530523	chr2:179395252;179395251;179395250
Novex-1	26424	79495;79496;79497	chr2:178530525;178530524;178530523	chr2:179395252;179395251;179395250
Novex-2	26491	79696;79697;79698	chr2:178530525;178530524;178530523	chr2:179395252;179395251;179395250
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: Ig-165
• Domain position: 79
• Structural Position: 162
• Q(SASA): 0.9301
• 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/D	rs1407917338	-0.233	0.434	N	0.304	0.084	0.209622950755	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/D	rs1407917338	-0.233	0.434	N	0.304	0.084	0.209622950755	gnomAD-4.0.0	6.56953E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.46994E-05	0	0
E/K	None	None	0.998	N	0.548	0.352	0.411665641125	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	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
E/A	0.177	likely_benign	0.1714	benign	0.004	Stabilizing	0.998	D	0.571	neutral	N	0.497485533	None	None	I
E/C	0.8881	likely_pathogenic	0.8823	pathogenic	-0.047	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	I
E/D	0.1178	likely_benign	0.1092	benign	-0.219	Destabilizing	0.434	N	0.304	neutral	N	0.510665474	None	None	I
E/F	0.7428	likely_pathogenic	0.7401	pathogenic	0.014	Stabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	I
E/G	0.1935	likely_benign	0.1816	benign	-0.126	Destabilizing	0.999	D	0.546	neutral	N	0.499352402	None	None	I
E/H	0.5645	likely_pathogenic	0.5319	ambiguous	0.506	Stabilizing	1.0	D	0.678	prob.neutral	None	None	None	None	I
E/I	0.3974	ambiguous	0.3992	ambiguous	0.29	Stabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	I
E/K	0.1594	likely_benign	0.1428	benign	0.565	Stabilizing	0.998	D	0.548	neutral	N	0.50173656	None	None	I
E/L	0.4548	ambiguous	0.4432	ambiguous	0.29	Stabilizing	1.0	D	0.678	prob.neutral	None	None	None	None	I
E/M	0.506	ambiguous	0.5041	ambiguous	0.131	Stabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	I
E/N	0.2696	likely_benign	0.2577	benign	0.254	Stabilizing	0.999	D	0.655	neutral	None	None	None	None	I
E/P	0.4867	ambiguous	0.4681	ambiguous	0.214	Stabilizing	1.0	D	0.633	neutral	None	None	None	None	I
E/Q	0.2072	likely_benign	0.187	benign	0.286	Stabilizing	0.999	D	0.583	neutral	D	0.524229417	None	None	I
E/R	0.291	likely_benign	0.2594	benign	0.732	Stabilizing	1.0	D	0.663	neutral	None	None	None	None	I
E/S	0.2178	likely_benign	0.2073	benign	0.137	Stabilizing	0.997	D	0.558	neutral	None	None	None	None	I
E/T	0.2507	likely_benign	0.2449	benign	0.256	Stabilizing	1.0	D	0.597	neutral	None	None	None	None	I
E/V	0.2543	likely_benign	0.2559	benign	0.214	Stabilizing	1.0	D	0.637	neutral	N	0.511185549	None	None	I
E/W	0.8875	likely_pathogenic	0.8795	pathogenic	0.075	Stabilizing	1.0	D	0.777	deleterious	None	None	None	None	I
E/Y	0.6603	likely_pathogenic	0.647	pathogenic	0.244	Stabilizing	1.0	D	0.683	prob.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.