TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1851	5776;5777;5778	chr2:178776313;178776312;178776311	chr2:179641040;179641039;179641038
N2AB	1851	5776;5777;5778	chr2:178776313;178776312;178776311	chr2:179641040;179641039;179641038
N2A	1851	5776;5777;5778	chr2:178776313;178776312;178776311	chr2:179641040;179641039;179641038
N2B	1805	5638;5639;5640	chr2:178776313;178776312;178776311	chr2:179641040;179641039;179641038
Novex-1	1805	5638;5639;5640	chr2:178776313;178776312;178776311	chr2:179641040;179641039;179641038
Novex-2	1805	5638;5639;5640	chr2:178776313;178776312;178776311	chr2:179641040;179641039;179641038
Novex-3	1851	5776;5777;5778	chr2:178776313;178776312;178776311	chr2:179641040;179641039;179641038

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Ig-9
• Domain position: 11
• Structural Position: 14
• Q(SASA): 0.5662
• 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/T	None	None	1.0	N	0.711	0.516	0.453772157364	gnomAD-4.0.0	9.60257E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.05E-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
R/A	0.6139	likely_pathogenic	0.5796	pathogenic	-0.134	Destabilizing	0.999	D	0.615	neutral	None	None	None	None	N
R/C	0.3793	ambiguous	0.3551	ambiguous	-0.267	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
R/D	0.8694	likely_pathogenic	0.8689	pathogenic	0.017	Stabilizing	1.0	D	0.714	prob.delet.	None	None	None	None	N
R/E	0.6099	likely_pathogenic	0.5866	pathogenic	0.111	Stabilizing	0.999	D	0.655	neutral	None	None	None	None	N
R/F	0.7968	likely_pathogenic	0.7848	pathogenic	-0.16	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
R/G	0.6142	likely_pathogenic	0.5838	pathogenic	-0.385	Destabilizing	1.0	D	0.661	neutral	D	0.533013696	None	None	N
R/H	0.1693	likely_benign	0.1586	benign	-0.792	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
R/I	0.5044	ambiguous	0.477	ambiguous	0.508	Stabilizing	1.0	D	0.729	prob.delet.	N	0.499314787	None	None	N
R/K	0.1521	likely_benign	0.1428	benign	-0.218	Destabilizing	0.997	D	0.555	neutral	N	0.50237116	None	None	N
R/L	0.4605	ambiguous	0.4183	ambiguous	0.508	Stabilizing	1.0	D	0.661	neutral	None	None	None	None	N
R/M	0.5328	ambiguous	0.4878	ambiguous	0.011	Stabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
R/N	0.7678	likely_pathogenic	0.769	pathogenic	0.08	Stabilizing	1.0	D	0.758	deleterious	None	None	None	None	N
R/P	0.917	likely_pathogenic	0.917	pathogenic	0.316	Stabilizing	1.0	D	0.694	prob.neutral	None	None	None	None	N
R/Q	0.1828	likely_benign	0.1671	benign	-0.017	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
R/S	0.6898	likely_pathogenic	0.6711	pathogenic	-0.387	Destabilizing	1.0	D	0.717	prob.delet.	N	0.488826372	None	None	N
R/T	0.4059	ambiguous	0.3652	ambiguous	-0.137	Destabilizing	1.0	D	0.711	prob.delet.	N	0.467020121	None	None	N
R/V	0.5158	ambiguous	0.4851	ambiguous	0.316	Stabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
R/W	0.4485	ambiguous	0.4046	ambiguous	-0.077	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
R/Y	0.6651	likely_pathogenic	0.6604	pathogenic	0.291	Stabilizing	1.0	D	0.719	prob.delet.	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.