TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31743	95452;95453;95454	chr2:178546009;178546008;178546007	chr2:179410736;179410735;179410734
N2AB	30102	90529;90530;90531	chr2:178546009;178546008;178546007	chr2:179410736;179410735;179410734
N2A	29175	87748;87749;87750	chr2:178546009;178546008;178546007	chr2:179410736;179410735;179410734
N2B	22678	68257;68258;68259	chr2:178546009;178546008;178546007	chr2:179410736;179410735;179410734
Novex-1	22803	68632;68633;68634	chr2:178546009;178546008;178546007	chr2:179410736;179410735;179410734
Novex-2	22870	68833;68834;68835	chr2:178546009;178546008;178546007	chr2:179410736;179410735;179410734
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: Fn3-119
• Domain position: 36
• Structural Position: 38
• Q(SASA): 0.1061
• 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/H	None	None	1.0	D	0.795	0.871	0.754091465348	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	3.66327E-05

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	0.9862	likely_pathogenic	0.9837	pathogenic	-3.441	Highly Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
Y/C	0.6898	likely_pathogenic	0.6255	pathogenic	-2.028	Highly Destabilizing	1.0	D	0.869	deleterious	D	0.676264818	None	None	N
Y/D	0.9946	likely_pathogenic	0.9937	pathogenic	-3.924	Highly Destabilizing	1.0	D	0.913	deleterious	D	0.676466622	None	None	N
Y/E	0.9983	likely_pathogenic	0.9978	pathogenic	-3.727	Highly Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
Y/F	0.1287	likely_benign	0.1217	benign	-1.38	Destabilizing	0.999	D	0.629	neutral	D	0.569288711	None	None	N
Y/G	0.9755	likely_pathogenic	0.9702	pathogenic	-3.825	Highly Destabilizing	1.0	D	0.924	deleterious	None	None	None	None	N
Y/H	0.9026	likely_pathogenic	0.8799	pathogenic	-2.51	Highly Destabilizing	1.0	D	0.795	deleterious	D	0.675861209	None	None	N
Y/I	0.9393	likely_pathogenic	0.9243	pathogenic	-2.137	Highly Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
Y/K	0.9964	likely_pathogenic	0.9959	pathogenic	-2.543	Highly Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
Y/L	0.8879	likely_pathogenic	0.8604	pathogenic	-2.137	Highly Destabilizing	0.999	D	0.758	deleterious	None	None	None	None	N
Y/M	0.9553	likely_pathogenic	0.9481	pathogenic	-1.836	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
Y/N	0.9579	likely_pathogenic	0.9498	pathogenic	-3.325	Highly Destabilizing	1.0	D	0.897	deleterious	D	0.676264818	None	None	N
Y/P	0.9982	likely_pathogenic	0.9981	pathogenic	-2.591	Highly Destabilizing	1.0	D	0.939	deleterious	None	None	None	None	N
Y/Q	0.9929	likely_pathogenic	0.9908	pathogenic	-3.094	Highly Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
Y/R	0.9836	likely_pathogenic	0.9801	pathogenic	-2.241	Highly Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
Y/S	0.9635	likely_pathogenic	0.9545	pathogenic	-3.602	Highly Destabilizing	1.0	D	0.903	deleterious	D	0.676264818	None	None	N
Y/T	0.9848	likely_pathogenic	0.9794	pathogenic	-3.296	Highly Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
Y/V	0.89	likely_pathogenic	0.8682	pathogenic	-2.591	Highly Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
Y/W	0.7575	likely_pathogenic	0.7461	pathogenic	-0.725	Destabilizing	1.0	D	0.787	deleterious	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.