TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24566	73921;73922;73923	chr2:178572436;178572435;178572434	chr2:179437163;179437162;179437161
N2AB	22925	68998;68999;69000	chr2:178572436;178572435;178572434	chr2:179437163;179437162;179437161
N2A	21998	66217;66218;66219	chr2:178572436;178572435;178572434	chr2:179437163;179437162;179437161
N2B	15501	46726;46727;46728	chr2:178572436;178572435;178572434	chr2:179437163;179437162;179437161
Novex-1	15626	47101;47102;47103	chr2:178572436;178572435;178572434	chr2:179437163;179437162;179437161
Novex-2	15693	47302;47303;47304	chr2:178572436;178572435;178572434	chr2:179437163;179437162;179437161
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-66
• Domain position: 48
• Structural Position: 65
• Q(SASA): 0.1731
• 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/C	rs748869822	-1.108	1.0	N	0.687	0.366	0.513394077459	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	6.54E-05	None	0	0	0
Y/C	rs748869822	-1.108	1.0	N	0.687	0.366	0.513394077459	gnomAD-4.0.0	3.1878E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.8673E-05	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
Y/A	0.9926	likely_pathogenic	0.9813	pathogenic	-2.813	Highly Destabilizing	0.999	D	0.625	neutral	None	None	None	None	N
Y/C	0.9047	likely_pathogenic	0.8073	pathogenic	-1.254	Destabilizing	1.0	D	0.687	prob.neutral	N	0.461285791	None	None	N
Y/D	0.9945	likely_pathogenic	0.988	pathogenic	-1.578	Destabilizing	1.0	D	0.729	prob.delet.	N	0.500835209	None	None	N
Y/E	0.9994	likely_pathogenic	0.9986	pathogenic	-1.495	Destabilizing	0.999	D	0.691	prob.neutral	None	None	None	None	N
Y/F	0.0975	likely_benign	0.0905	benign	-1.375	Destabilizing	0.872	D	0.505	neutral	N	0.454368608	None	None	N
Y/G	0.9923	likely_pathogenic	0.9809	pathogenic	-3.119	Highly Destabilizing	0.999	D	0.707	prob.neutral	None	None	None	None	N
Y/H	0.927	likely_pathogenic	0.875	pathogenic	-1.288	Destabilizing	0.999	D	0.651	neutral	N	0.479136557	None	None	N
Y/I	0.9863	likely_pathogenic	0.9714	pathogenic	-1.866	Destabilizing	0.976	D	0.675	prob.neutral	None	None	None	None	N
Y/K	0.9992	likely_pathogenic	0.9983	pathogenic	-1.364	Destabilizing	0.992	D	0.687	prob.neutral	None	None	None	None	N
Y/L	0.9686	likely_pathogenic	0.945	pathogenic	-1.866	Destabilizing	0.854	D	0.566	neutral	None	None	None	None	N
Y/M	0.9876	likely_pathogenic	0.9773	pathogenic	-1.455	Destabilizing	1.0	D	0.674	neutral	None	None	None	None	N
Y/N	0.9766	likely_pathogenic	0.9488	pathogenic	-1.624	Destabilizing	1.0	D	0.693	prob.neutral	N	0.478376088	None	None	N
Y/P	0.9951	likely_pathogenic	0.9912	pathogenic	-2.181	Highly Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
Y/Q	0.9982	likely_pathogenic	0.9959	pathogenic	-1.671	Destabilizing	0.999	D	0.674	neutral	None	None	None	None	N
Y/R	0.9965	likely_pathogenic	0.993	pathogenic	-0.715	Destabilizing	0.998	D	0.693	prob.neutral	None	None	None	None	N
Y/S	0.9714	likely_pathogenic	0.9371	pathogenic	-2.195	Highly Destabilizing	0.999	D	0.701	prob.neutral	N	0.468398908	None	None	N
Y/T	0.9952	likely_pathogenic	0.9884	pathogenic	-2.025	Highly Destabilizing	0.999	D	0.699	prob.neutral	None	None	None	None	N
Y/V	0.9758	likely_pathogenic	0.9503	pathogenic	-2.181	Highly Destabilizing	0.999	D	0.618	neutral	None	None	None	None	N
Y/W	0.303	likely_benign	0.2709	benign	-0.803	Destabilizing	0.378	N	0.251	neutral	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.