TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24515	73768;73769;73770	chr2:178572589;178572588;178572587	chr2:179437316;179437315;179437314
N2AB	22874	68845;68846;68847	chr2:178572589;178572588;178572587	chr2:179437316;179437315;179437314
N2A	21947	66064;66065;66066	chr2:178572589;178572588;178572587	chr2:179437316;179437315;179437314
N2B	15450	46573;46574;46575	chr2:178572589;178572588;178572587	chr2:179437316;179437315;179437314
Novex-1	15575	46948;46949;46950	chr2:178572589;178572588;178572587	chr2:179437316;179437315;179437314
Novex-2	15642	47149;47150;47151	chr2:178572589;178572588;178572587	chr2:179437316;179437315;179437314
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Ig-132
• Domain position: 85
• Structural Position: 175
• Q(SASA): 0.647
• Predicted PPI site: I

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	rs1470812776	None	0.892	N	0.617	0.328	0.492749560936	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
R/T	rs1470812776	None	0.892	N	0.617	0.328	0.492749560936	gnomAD-4.0.0	1.85954E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.54322E-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
R/A	0.8958	likely_pathogenic	0.9106	pathogenic	-0.518	Destabilizing	0.916	D	0.619	neutral	None	None	None	None	I
R/C	0.4414	ambiguous	0.4742	ambiguous	-0.605	Destabilizing	0.999	D	0.747	deleterious	None	None	None	None	I
R/D	0.9703	likely_pathogenic	0.9723	pathogenic	0.067	Stabilizing	0.95	D	0.586	neutral	None	None	None	None	I
R/E	0.8498	likely_pathogenic	0.8627	pathogenic	0.191	Stabilizing	0.916	D	0.605	neutral	None	None	None	None	I
R/F	0.9197	likely_pathogenic	0.9351	pathogenic	-0.385	Destabilizing	0.996	D	0.718	prob.delet.	None	None	None	None	I
R/G	0.8842	likely_pathogenic	0.8987	pathogenic	-0.81	Destabilizing	0.805	D	0.603	neutral	N	0.511051967	None	None	I
R/H	0.2175	likely_benign	0.2555	benign	-1.099	Destabilizing	0.987	D	0.64	neutral	None	None	None	None	I
R/I	0.702	likely_pathogenic	0.7268	pathogenic	0.255	Stabilizing	0.983	D	0.721	prob.delet.	N	0.502139204	None	None	I
R/K	0.1215	likely_benign	0.1347	benign	-0.522	Destabilizing	0.773	D	0.548	neutral	N	0.435239422	None	None	I
R/L	0.6538	likely_pathogenic	0.6863	pathogenic	0.255	Stabilizing	0.987	D	0.583	neutral	None	None	None	None	I
R/M	0.6875	likely_pathogenic	0.7251	pathogenic	-0.229	Destabilizing	0.999	D	0.642	neutral	None	None	None	None	I
R/N	0.9189	likely_pathogenic	0.9332	pathogenic	-0.188	Destabilizing	0.033	N	0.378	neutral	None	None	None	None	I
R/P	0.9941	likely_pathogenic	0.9939	pathogenic	0.019	Stabilizing	0.996	D	0.701	prob.neutral	None	None	None	None	I
R/Q	0.2434	likely_benign	0.2687	benign	-0.279	Destabilizing	0.975	D	0.635	neutral	None	None	None	None	I
R/S	0.9188	likely_pathogenic	0.9323	pathogenic	-0.847	Destabilizing	0.805	D	0.636	neutral	N	0.493191647	None	None	I
R/T	0.7333	likely_pathogenic	0.7706	pathogenic	-0.544	Destabilizing	0.892	D	0.617	neutral	N	0.495037087	None	None	I
R/V	0.7518	likely_pathogenic	0.7757	pathogenic	0.019	Stabilizing	0.987	D	0.713	prob.delet.	None	None	None	None	I
R/W	0.5416	ambiguous	0.5815	pathogenic	-0.151	Destabilizing	0.999	D	0.742	deleterious	None	None	None	None	I
R/Y	0.8017	likely_pathogenic	0.8311	pathogenic	0.164	Stabilizing	0.996	D	0.707	prob.neutral	None	None	None	None	I

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.