TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6430	19513;19514;19515	chr2:178728638;178728637;178728636	chr2:179593365;179593364;179593363
N2AB	6113	18562;18563;18564	chr2:178728638;178728637;178728636	chr2:179593365;179593364;179593363
N2A	5186	15781;15782;15783	chr2:178728638;178728637;178728636	chr2:179593365;179593364;179593363
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: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-48
• Domain position: 46
• Structural Position: 115
• Q(SASA): 0.6046
• 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
Y/C	rs781726929	-0.198	0.997	N	0.363	0.423	0.430808444494	gnomAD-2.1.1	1.61E-05	None	None	None	None	N	None	0	0	None	0	2.23989E-04	None	0	None	0	0	0
Y/C	rs781726929	-0.198	0.997	N	0.363	0.423	0.430808444494	gnomAD-4.0.0	2.7377E-06	None	None	None	None	N	None	0	0	None	0	5.04898E-05	None	0	0	1.79923E-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
Y/A	0.6401	likely_pathogenic	0.5933	pathogenic	-1.993	Destabilizing	0.688	D	0.315	neutral	None	None	None	None	N
Y/C	0.3032	likely_benign	0.2583	benign	-0.959	Destabilizing	0.997	D	0.363	neutral	N	0.509906886	None	None	N
Y/D	0.4251	ambiguous	0.325	benign	-0.682	Destabilizing	0.801	D	0.422	neutral	N	0.406606373	None	None	N
Y/E	0.7784	likely_pathogenic	0.7047	pathogenic	-0.551	Destabilizing	0.525	D	0.337	neutral	None	None	None	None	N
Y/F	0.1677	likely_benign	0.16	benign	-0.677	Destabilizing	0.012	N	0.16	neutral	N	0.417804801	None	None	N
Y/G	0.6023	likely_pathogenic	0.5397	ambiguous	-2.339	Highly Destabilizing	0.915	D	0.389	neutral	None	None	None	None	N
Y/H	0.2878	likely_benign	0.2357	benign	-0.819	Destabilizing	0.966	D	0.404	neutral	N	0.410012037	None	None	N
Y/I	0.6161	likely_pathogenic	0.5697	pathogenic	-0.933	Destabilizing	0.728	D	0.408	neutral	None	None	None	None	N
Y/K	0.6707	likely_pathogenic	0.6094	pathogenic	-1.065	Destabilizing	0.067	N	0.279	neutral	None	None	None	None	N
Y/L	0.5754	likely_pathogenic	0.5429	ambiguous	-0.933	Destabilizing	0.525	D	0.306	neutral	None	None	None	None	N
Y/M	0.7491	likely_pathogenic	0.7332	pathogenic	-0.745	Destabilizing	0.974	D	0.385	neutral	None	None	None	None	N
Y/N	0.2556	likely_benign	0.194	benign	-1.542	Destabilizing	0.891	D	0.396	neutral	N	0.41945824	None	None	N
Y/P	0.8779	likely_pathogenic	0.857	pathogenic	-1.283	Destabilizing	0.991	D	0.428	neutral	None	None	None	None	N
Y/Q	0.6319	likely_pathogenic	0.5575	ambiguous	-1.343	Destabilizing	0.08	N	0.197	neutral	None	None	None	None	N
Y/R	0.5232	ambiguous	0.4466	ambiguous	-0.839	Destabilizing	0.728	D	0.383	neutral	None	None	None	None	N
Y/S	0.3378	likely_benign	0.2813	benign	-2.104	Highly Destabilizing	0.801	D	0.347	neutral	N	0.42105575	None	None	N
Y/T	0.5981	likely_pathogenic	0.5373	ambiguous	-1.865	Destabilizing	0.915	D	0.387	neutral	None	None	None	None	N
Y/V	0.5207	ambiguous	0.4822	ambiguous	-1.283	Destabilizing	0.842	D	0.335	neutral	None	None	None	None	N
Y/W	0.6195	likely_pathogenic	0.5962	pathogenic	-0.247	Destabilizing	0.991	D	0.385	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.