TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6203	18832;18833;18834	chr2:178729549;178729548;178729547	chr2:179594276;179594275;179594274
N2AB	5886	17881;17882;17883	chr2:178729549;178729548;178729547	chr2:179594276;179594275;179594274
N2A	4959	15100;15101;15102	chr2:178729549;178729548;178729547	chr2:179594276;179594275;179594274
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Ig-46
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.6795
• 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
R/G	None	None	0.801	N	0.382	0.43	0.564503807532	gnomAD-4.0.0	1.59392E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86331E-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
R/A	0.32	likely_benign	0.383	ambiguous	-0.585	Destabilizing	0.525	D	0.334	neutral	None	None	None	None	I
R/C	0.1992	likely_benign	0.2397	benign	-0.504	Destabilizing	0.998	D	0.298	neutral	None	None	None	None	I
R/D	0.5573	ambiguous	0.6231	pathogenic	0.043	Stabilizing	0.842	D	0.423	neutral	None	None	None	None	I
R/E	0.2545	likely_benign	0.2884	benign	0.187	Stabilizing	0.525	D	0.319	neutral	None	None	None	None	I
R/F	0.5581	ambiguous	0.6286	pathogenic	-0.272	Destabilizing	0.974	D	0.323	neutral	None	None	None	None	I
R/G	0.1974	likely_benign	0.2419	benign	-0.92	Destabilizing	0.801	D	0.382	neutral	N	0.500785298	None	None	I
R/H	0.0995	likely_benign	0.1077	benign	-1.269	Destabilizing	0.974	D	0.279	neutral	None	None	None	None	I
R/I	0.2753	likely_benign	0.3306	benign	0.318	Stabilizing	0.934	D	0.374	neutral	N	0.501947203	None	None	I
R/K	0.0849	likely_benign	0.092	benign	-0.599	Destabilizing	0.022	N	0.119	neutral	N	0.411114555	None	None	I
R/L	0.2456	likely_benign	0.2943	benign	0.318	Stabilizing	0.728	D	0.375	neutral	None	None	None	None	I
R/M	0.2542	likely_benign	0.3041	benign	-0.136	Destabilizing	0.991	D	0.301	neutral	None	None	None	None	I
R/N	0.4417	ambiguous	0.492	ambiguous	-0.152	Destabilizing	0.842	D	0.27	neutral	None	None	None	None	I
R/P	0.861	likely_pathogenic	0.8964	pathogenic	0.039	Stabilizing	0.974	D	0.39	neutral	None	None	None	None	I
R/Q	0.0898	likely_benign	0.0961	benign	-0.222	Destabilizing	0.172	N	0.161	neutral	None	None	None	None	I
R/S	0.3445	ambiguous	0.3949	ambiguous	-0.834	Destabilizing	0.454	N	0.336	neutral	N	0.482553366	None	None	I
R/T	0.1464	likely_benign	0.1769	benign	-0.499	Destabilizing	0.051	N	0.187	neutral	N	0.464543608	None	None	I
R/V	0.3312	likely_benign	0.3896	ambiguous	0.039	Stabilizing	0.728	D	0.423	neutral	None	None	None	None	I
R/W	0.1744	likely_benign	0.1903	benign	0.035	Stabilizing	0.998	D	0.296	neutral	None	None	None	None	I
R/Y	0.3944	ambiguous	0.4499	ambiguous	0.314	Stabilizing	0.991	D	0.348	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.