TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30743	92452;92453;92454	chr2:178549399;178549398;178549397	chr2:179414126;179414125;179414124
N2AB	29102	87529;87530;87531	chr2:178549399;178549398;178549397	chr2:179414126;179414125;179414124
N2A	28175	84748;84749;84750	chr2:178549399;178549398;178549397	chr2:179414126;179414125;179414124
N2B	21678	65257;65258;65259	chr2:178549399;178549398;178549397	chr2:179414126;179414125;179414124
Novex-1	21803	65632;65633;65634	chr2:178549399;178549398;178549397	chr2:179414126;179414125;179414124
Novex-2	21870	65833;65834;65835	chr2:178549399;178549398;178549397	chr2:179414126;179414125;179414124
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-112
• Domain position: 25
• Structural Position: 27
• Q(SASA): 0.161
• 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
P/R	rs771621337	-0.906	1.0	D	0.908	0.731	0.829251667788	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
P/R	rs771621337	-0.906	1.0	D	0.908	0.731	0.829251667788	gnomAD-4.0.0	3.18291E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	2.41313E-04	2.85843E-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
P/A	0.9365	likely_pathogenic	0.9324	pathogenic	-1.989	Destabilizing	1.0	D	0.841	deleterious	D	0.598312882	None	None	N
P/C	0.9944	likely_pathogenic	0.994	pathogenic	-1.426	Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	N
P/D	0.999	likely_pathogenic	0.9991	pathogenic	-2.014	Highly Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
P/E	0.9976	likely_pathogenic	0.9976	pathogenic	-1.986	Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
P/F	0.9996	likely_pathogenic	0.9997	pathogenic	-1.574	Destabilizing	1.0	D	0.909	deleterious	None	None	None	None	N
P/G	0.9907	likely_pathogenic	0.9901	pathogenic	-2.361	Highly Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
P/H	0.9968	likely_pathogenic	0.9971	pathogenic	-1.89	Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
P/I	0.9963	likely_pathogenic	0.9964	pathogenic	-1.036	Destabilizing	1.0	D	0.904	deleterious	None	None	None	None	N
P/K	0.9982	likely_pathogenic	0.9983	pathogenic	-1.729	Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
P/L	0.9793	likely_pathogenic	0.9782	pathogenic	-1.036	Destabilizing	1.0	D	0.921	deleterious	D	0.63969891	None	None	N
P/M	0.9968	likely_pathogenic	0.997	pathogenic	-0.756	Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
P/N	0.9986	likely_pathogenic	0.9987	pathogenic	-1.535	Destabilizing	1.0	D	0.908	deleterious	None	None	None	None	N
P/Q	0.9957	likely_pathogenic	0.9958	pathogenic	-1.687	Destabilizing	1.0	D	0.875	deleterious	D	0.640707932	None	None	N
P/R	0.995	likely_pathogenic	0.9948	pathogenic	-1.164	Destabilizing	1.0	D	0.908	deleterious	D	0.640506128	None	None	N
P/S	0.9851	likely_pathogenic	0.9865	pathogenic	-2.082	Highly Destabilizing	1.0	D	0.885	deleterious	D	0.578407442	None	None	N
P/T	0.979	likely_pathogenic	0.9797	pathogenic	-1.935	Destabilizing	1.0	D	0.888	deleterious	D	0.617320023	None	None	N
P/V	0.9882	likely_pathogenic	0.9881	pathogenic	-1.321	Destabilizing	1.0	D	0.919	deleterious	None	None	None	None	N
P/W	0.9997	likely_pathogenic	0.9998	pathogenic	-1.78	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
P/Y	0.9996	likely_pathogenic	0.9996	pathogenic	-1.53	Destabilizing	1.0	D	0.915	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.