TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26441	79546;79547;79548	chr2:178566811;178566810;178566809	chr2:179431538;179431537;179431536
N2AB	24800	74623;74624;74625	chr2:178566811;178566810;178566809	chr2:179431538;179431537;179431536
N2A	23873	71842;71843;71844	chr2:178566811;178566810;178566809	chr2:179431538;179431537;179431536
N2B	17376	52351;52352;52353	chr2:178566811;178566810;178566809	chr2:179431538;179431537;179431536
Novex-1	17501	52726;52727;52728	chr2:178566811;178566810;178566809	chr2:179431538;179431537;179431536
Novex-2	17568	52927;52928;52929	chr2:178566811;178566810;178566809	chr2:179431538;179431537;179431536
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-80
• Domain position: 56
• Structural Position: 77
• Q(SASA): 0.13
• 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
I/V	rs1305096924	None	0.001	N	0.167	0.04	0.303123707472	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
I/V	rs1305096924	None	0.001	N	0.167	0.04	0.303123707472	gnomAD-4.0.0	6.57341E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47037E-05	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	0.7177	likely_pathogenic	0.7675	pathogenic	-1.74	Destabilizing	0.415	N	0.468	neutral	None	None	None	None	N
I/C	0.7835	likely_pathogenic	0.8157	pathogenic	-1.099	Destabilizing	0.996	D	0.625	neutral	None	None	None	None	N
I/D	0.979	likely_pathogenic	0.9875	pathogenic	-0.916	Destabilizing	0.987	D	0.683	prob.neutral	None	None	None	None	N
I/E	0.9505	likely_pathogenic	0.967	pathogenic	-0.818	Destabilizing	0.961	D	0.655	neutral	None	None	None	None	N
I/F	0.5315	ambiguous	0.6378	pathogenic	-1.022	Destabilizing	0.901	D	0.557	neutral	N	0.473241662	None	None	N
I/G	0.9118	likely_pathogenic	0.939	pathogenic	-2.158	Highly Destabilizing	0.961	D	0.633	neutral	None	None	None	None	N
I/H	0.9199	likely_pathogenic	0.9536	pathogenic	-1.432	Destabilizing	0.996	D	0.705	prob.neutral	None	None	None	None	N
I/K	0.9202	likely_pathogenic	0.9473	pathogenic	-1.014	Destabilizing	0.961	D	0.661	neutral	None	None	None	None	N
I/L	0.1426	likely_benign	0.1798	benign	-0.621	Destabilizing	0.19	N	0.285	neutral	N	0.457662416	None	None	N
I/M	0.181	likely_benign	0.2186	benign	-0.606	Destabilizing	0.901	D	0.603	neutral	N	0.4946376	None	None	N
I/N	0.7383	likely_pathogenic	0.8163	pathogenic	-0.98	Destabilizing	0.983	D	0.707	prob.neutral	N	0.464337211	None	None	N
I/P	0.9445	likely_pathogenic	0.9533	pathogenic	-0.965	Destabilizing	0.987	D	0.685	prob.neutral	None	None	None	None	N
I/Q	0.8886	likely_pathogenic	0.9259	pathogenic	-1.004	Destabilizing	0.987	D	0.709	prob.delet.	None	None	None	None	N
I/R	0.9043	likely_pathogenic	0.9351	pathogenic	-0.667	Destabilizing	0.961	D	0.708	prob.delet.	None	None	None	None	N
I/S	0.7532	likely_pathogenic	0.8237	pathogenic	-1.737	Destabilizing	0.901	D	0.596	neutral	N	0.488289181	None	None	N
I/T	0.6128	likely_pathogenic	0.6784	pathogenic	-1.503	Destabilizing	0.722	D	0.502	neutral	N	0.505930792	None	None	N
I/V	0.0804	likely_benign	0.0797	benign	-0.965	Destabilizing	0.001	N	0.167	neutral	N	0.392880219	None	None	N
I/W	0.9677	likely_pathogenic	0.9801	pathogenic	-1.172	Destabilizing	0.996	D	0.726	prob.delet.	None	None	None	None	N
I/Y	0.8946	likely_pathogenic	0.9339	pathogenic	-0.889	Destabilizing	0.961	D	0.633	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.