TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19512	58759;58760;58761	chr2:178593766;178593765;178593764	chr2:179458493;179458492;179458491
N2AB	17871	53836;53837;53838	chr2:178593766;178593765;178593764	chr2:179458493;179458492;179458491
N2A	16944	51055;51056;51057	chr2:178593766;178593765;178593764	chr2:179458493;179458492;179458491
N2B	10447	31564;31565;31566	chr2:178593766;178593765;178593764	chr2:179458493;179458492;179458491
Novex-1	10572	31939;31940;31941	chr2:178593766;178593765;178593764	chr2:179458493;179458492;179458491
Novex-2	10639	32140;32141;32142	chr2:178593766;178593765;178593764	chr2:179458493;179458492;179458491
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Fn3-29
• Domain position: 34
• Structural Position: 35
• Q(SASA): 0.1845
• 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
I/T	rs1343150103	-2.227	0.822	D	0.807	0.545	0.768437955185	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	0	2.91E-05	None	0	0	None	0	None	0	0	0
I/T	rs1343150103	-2.227	0.822	D	0.807	0.545	0.768437955185	gnomAD-4.0.0	1.59241E-06	None	None	None	None	I	None	0	2.28959E-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
I/A	0.976	likely_pathogenic	0.9693	pathogenic	-2.146	Highly Destabilizing	0.86	D	0.717	prob.delet.	None	None	None	None	I
I/C	0.9844	likely_pathogenic	0.9797	pathogenic	-1.41	Destabilizing	0.998	D	0.757	deleterious	None	None	None	None	I
I/D	0.9962	likely_pathogenic	0.9959	pathogenic	-1.686	Destabilizing	0.993	D	0.863	deleterious	None	None	None	None	I
I/E	0.988	likely_pathogenic	0.988	pathogenic	-1.653	Destabilizing	0.978	D	0.863	deleterious	None	None	None	None	I
I/F	0.9323	likely_pathogenic	0.9325	pathogenic	-1.607	Destabilizing	0.942	D	0.697	prob.neutral	D	0.540995236	None	None	I
I/G	0.9947	likely_pathogenic	0.9936	pathogenic	-2.521	Highly Destabilizing	0.978	D	0.859	deleterious	None	None	None	None	I
I/H	0.9956	likely_pathogenic	0.9956	pathogenic	-1.704	Destabilizing	0.998	D	0.831	deleterious	None	None	None	None	I
I/K	0.9848	likely_pathogenic	0.9841	pathogenic	-1.483	Destabilizing	0.978	D	0.861	deleterious	None	None	None	None	I
I/L	0.5	ambiguous	0.5352	ambiguous	-1.159	Destabilizing	0.006	N	0.221	neutral	D	0.52339155	None	None	I
I/M	0.5687	likely_pathogenic	0.558	ambiguous	-0.842	Destabilizing	0.942	D	0.676	prob.neutral	D	0.532173826	None	None	I
I/N	0.9415	likely_pathogenic	0.9372	pathogenic	-1.337	Destabilizing	0.99	D	0.863	deleterious	D	0.54454409	None	None	I
I/P	0.9617	likely_pathogenic	0.9451	pathogenic	-1.459	Destabilizing	0.993	D	0.868	deleterious	None	None	None	None	I
I/Q	0.9897	likely_pathogenic	0.9895	pathogenic	-1.51	Destabilizing	0.993	D	0.86	deleterious	None	None	None	None	I
I/R	0.9837	likely_pathogenic	0.9835	pathogenic	-0.849	Destabilizing	0.978	D	0.866	deleterious	None	None	None	None	I
I/S	0.977	likely_pathogenic	0.9717	pathogenic	-2.025	Highly Destabilizing	0.97	D	0.833	deleterious	D	0.543783621	None	None	I
I/T	0.9518	likely_pathogenic	0.9386	pathogenic	-1.866	Destabilizing	0.822	D	0.807	deleterious	D	0.525679366	None	None	I
I/V	0.1929	likely_benign	0.1395	benign	-1.459	Destabilizing	0.058	N	0.233	neutral	N	0.513097199	None	None	I
I/W	0.9977	likely_pathogenic	0.9976	pathogenic	-1.69	Destabilizing	0.998	D	0.817	deleterious	None	None	None	None	I
I/Y	0.9855	likely_pathogenic	0.9848	pathogenic	-1.487	Destabilizing	0.978	D	0.784	deleterious	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.