TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23806	71641;71642;71643	chr2:178574716;178574715;178574714	chr2:179439443;179439442;179439441
N2AB	22165	66718;66719;66720	chr2:178574716;178574715;178574714	chr2:179439443;179439442;179439441
N2A	21238	63937;63938;63939	chr2:178574716;178574715;178574714	chr2:179439443;179439442;179439441
N2B	14741	44446;44447;44448	chr2:178574716;178574715;178574714	chr2:179439443;179439442;179439441
Novex-1	14866	44821;44822;44823	chr2:178574716;178574715;178574714	chr2:179439443;179439442;179439441
Novex-2	14933	45022;45023;45024	chr2:178574716;178574715;178574714	chr2:179439443;179439442;179439441
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: Fn3-60
• Domain position: 81
• Structural Position: 113
• Q(SASA): 0.782
• 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/I	None	None	0.991	N	0.596	0.41	0.675195094354	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
R/T	None	None	0.969	N	0.521	0.406	0.60163206408	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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	0.9786	likely_pathogenic	0.9704	pathogenic	0.069	Stabilizing	0.953	D	0.581	neutral	None	None	None	None	I
R/C	0.8399	likely_pathogenic	0.8045	pathogenic	-0.189	Destabilizing	0.999	D	0.659	neutral	None	None	None	None	I
R/D	0.9934	likely_pathogenic	0.9906	pathogenic	-0.277	Destabilizing	0.06	N	0.525	neutral	None	None	None	None	I
R/E	0.9753	likely_pathogenic	0.9661	pathogenic	-0.198	Destabilizing	0.91	D	0.52	neutral	None	None	None	None	I
R/F	0.9844	likely_pathogenic	0.981	pathogenic	-0.181	Destabilizing	0.998	D	0.597	neutral	None	None	None	None	I
R/G	0.9682	likely_pathogenic	0.9524	pathogenic	-0.12	Destabilizing	0.939	D	0.553	neutral	N	0.509816459	None	None	I
R/H	0.6569	likely_pathogenic	0.5918	pathogenic	-0.877	Destabilizing	0.998	D	0.489	neutral	None	None	None	None	I
R/I	0.9106	likely_pathogenic	0.8969	pathogenic	0.533	Stabilizing	0.991	D	0.596	neutral	N	0.472439868	None	None	I
R/K	0.5298	ambiguous	0.4728	ambiguous	-0.044	Destabilizing	0.863	D	0.483	neutral	N	0.450677729	None	None	I
R/L	0.9095	likely_pathogenic	0.8914	pathogenic	0.533	Stabilizing	0.993	D	0.488	neutral	None	None	None	None	I
R/M	0.956	likely_pathogenic	0.9479	pathogenic	-0.067	Destabilizing	0.999	D	0.522	neutral	None	None	None	None	I
R/N	0.9853	likely_pathogenic	0.9794	pathogenic	-0.015	Destabilizing	0.91	D	0.515	neutral	None	None	None	None	I
R/P	0.9788	likely_pathogenic	0.9642	pathogenic	0.399	Stabilizing	0.993	D	0.575	neutral	None	None	None	None	I
R/Q	0.6871	likely_pathogenic	0.6016	pathogenic	0.006	Stabilizing	0.993	D	0.496	neutral	None	None	None	None	I
R/S	0.9842	likely_pathogenic	0.9758	pathogenic	-0.191	Destabilizing	0.939	D	0.563	neutral	N	0.468532771	None	None	I
R/T	0.9674	likely_pathogenic	0.9516	pathogenic	0.025	Stabilizing	0.969	D	0.521	neutral	N	0.501682552	None	None	I
R/V	0.9546	likely_pathogenic	0.9395	pathogenic	0.399	Stabilizing	0.993	D	0.593	neutral	None	None	None	None	I
R/W	0.8598	likely_pathogenic	0.8352	pathogenic	-0.355	Destabilizing	0.999	D	0.68	prob.neutral	None	None	None	None	I
R/Y	0.9439	likely_pathogenic	0.9307	pathogenic	0.072	Stabilizing	0.998	D	0.579	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.