TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1778	5557;5558;5559	chr2:178776532;178776531;178776530	chr2:179641259;179641258;179641257
N2AB	1778	5557;5558;5559	chr2:178776532;178776531;178776530	chr2:179641259;179641258;179641257
N2A	1778	5557;5558;5559	chr2:178776532;178776531;178776530	chr2:179641259;179641258;179641257
N2B	1732	5419;5420;5421	chr2:178776532;178776531;178776530	chr2:179641259;179641258;179641257
Novex-1	1732	5419;5420;5421	chr2:178776532;178776531;178776530	chr2:179641259;179641258;179641257
Novex-2	1732	5419;5420;5421	chr2:178776532;178776531;178776530	chr2:179641259;179641258;179641257
Novex-3	1778	5557;5558;5559	chr2:178776532;178776531;178776530	chr2:179641259;179641258;179641257

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Ig-8
• Domain position: 76
• Structural Position: 157
• Q(SASA): 0.3438
• 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
R/K	None	None	0.997	N	0.553	0.369	0.311387274539	gnomAD-4.0.0	1.60005E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02334E-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
R/A	0.9089	likely_pathogenic	0.9275	pathogenic	-0.997	Destabilizing	0.999	D	0.69	prob.neutral	None	None	None	None	N
R/C	0.5723	likely_pathogenic	0.6052	pathogenic	-0.908	Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
R/D	0.9873	likely_pathogenic	0.991	pathogenic	-0.384	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
R/E	0.8317	likely_pathogenic	0.8636	pathogenic	-0.243	Destabilizing	0.999	D	0.697	prob.neutral	None	None	None	None	N
R/F	0.9436	likely_pathogenic	0.9558	pathogenic	-0.7	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
R/G	0.9249	likely_pathogenic	0.9417	pathogenic	-1.338	Destabilizing	1.0	D	0.822	deleterious	D	0.667630198	None	None	N
R/H	0.2731	likely_benign	0.3079	benign	-1.533	Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	N
R/I	0.6634	likely_pathogenic	0.7114	pathogenic	-0.061	Destabilizing	1.0	D	0.86	deleterious	N	0.501573347	None	None	N
R/K	0.169	likely_benign	0.1861	benign	-1.108	Destabilizing	0.997	D	0.553	neutral	N	0.495396009	None	None	N
R/L	0.6789	likely_pathogenic	0.7311	pathogenic	-0.061	Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	N
R/M	0.7696	likely_pathogenic	0.8138	pathogenic	-0.315	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
R/N	0.9534	likely_pathogenic	0.9664	pathogenic	-0.602	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
R/P	0.9982	likely_pathogenic	0.9984	pathogenic	-0.354	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
R/Q	0.2312	likely_benign	0.2639	benign	-0.712	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
R/S	0.923	likely_pathogenic	0.9429	pathogenic	-1.354	Destabilizing	1.0	D	0.821	deleterious	N	0.501101023	None	None	N
R/T	0.7159	likely_pathogenic	0.7664	pathogenic	-1.024	Destabilizing	1.0	D	0.815	deleterious	N	0.50896261	None	None	N
R/V	0.7096	likely_pathogenic	0.7526	pathogenic	-0.354	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
R/W	0.7169	likely_pathogenic	0.7563	pathogenic	-0.318	Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	N
R/Y	0.8703	likely_pathogenic	0.8976	pathogenic	-0.038	Destabilizing	1.0	D	0.869	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.