TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5331	16216;16217;16218	chr2:178733302;178733301;178733300	chr2:179598029;179598028;179598027
N2AB	5014	15265;15266;15267	chr2:178733302;178733301;178733300	chr2:179598029;179598028;179598027
N2A	4087	12484;12485;12486	chr2:178733302;178733301;178733300	chr2:179598029;179598028;179598027
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-36
• Domain position: 71
• Structural Position: 154
• Q(SASA): 0.098
• 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	rs369924189	-0.998	0.999	D	0.824	0.785	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
Y/C	rs369924189	-0.998	0.999	D	0.824	0.785	None	gnomAD-4.0.0	2.56281E-06	None	None	None	None	N	None	3.38123E-05	0	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
Y/A	0.9949	likely_pathogenic	0.9942	pathogenic	-2.52	Highly Destabilizing	0.953	D	0.794	deleterious	None	None	None	None	N
Y/C	0.9288	likely_pathogenic	0.9139	pathogenic	-1.991	Destabilizing	0.999	D	0.824	deleterious	D	0.661316994	None	None	N
Y/D	0.9967	likely_pathogenic	0.9969	pathogenic	-3.005	Highly Destabilizing	0.997	D	0.859	deleterious	D	0.661316994	None	None	N
Y/E	0.9984	likely_pathogenic	0.9983	pathogenic	-2.758	Highly Destabilizing	0.998	D	0.828	deleterious	None	None	None	None	N
Y/F	0.3254	likely_benign	0.2962	benign	-0.924	Destabilizing	0.939	D	0.672	neutral	D	0.599662996	None	None	N
Y/G	0.9892	likely_pathogenic	0.9888	pathogenic	-2.984	Highly Destabilizing	0.998	D	0.855	deleterious	None	None	None	None	N
Y/H	0.9761	likely_pathogenic	0.9749	pathogenic	-2.178	Highly Destabilizing	0.997	D	0.706	prob.neutral	D	0.66111519	None	None	N
Y/I	0.911	likely_pathogenic	0.873	pathogenic	-0.985	Destabilizing	0.128	N	0.63	neutral	None	None	None	None	N
Y/K	0.9983	likely_pathogenic	0.9983	pathogenic	-2.012	Highly Destabilizing	0.993	D	0.83	deleterious	None	None	None	None	N
Y/L	0.8414	likely_pathogenic	0.7939	pathogenic	-0.985	Destabilizing	0.807	D	0.743	deleterious	None	None	None	None	N
Y/M	0.9646	likely_pathogenic	0.9546	pathogenic	-1.126	Destabilizing	0.996	D	0.758	deleterious	None	None	None	None	N
Y/N	0.978	likely_pathogenic	0.9789	pathogenic	-2.91	Highly Destabilizing	0.997	D	0.839	deleterious	D	0.661316994	None	None	N
Y/P	0.9989	likely_pathogenic	0.9989	pathogenic	-1.513	Destabilizing	0.998	D	0.863	deleterious	None	None	None	None	N
Y/Q	0.998	likely_pathogenic	0.998	pathogenic	-2.493	Highly Destabilizing	0.998	D	0.752	deleterious	None	None	None	None	N
Y/R	0.9951	likely_pathogenic	0.9952	pathogenic	-2.156	Highly Destabilizing	0.998	D	0.834	deleterious	None	None	None	None	N
Y/S	0.9912	likely_pathogenic	0.9911	pathogenic	-3.292	Highly Destabilizing	0.991	D	0.826	deleterious	D	0.661316994	None	None	N
Y/T	0.9953	likely_pathogenic	0.9946	pathogenic	-2.896	Highly Destabilizing	0.986	D	0.82	deleterious	None	None	None	None	N
Y/V	0.8729	likely_pathogenic	0.8352	pathogenic	-1.513	Destabilizing	0.91	D	0.75	deleterious	None	None	None	None	N
Y/W	0.8973	likely_pathogenic	0.8975	pathogenic	-0.274	Destabilizing	0.999	D	0.7	prob.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.