TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5192	15799;15800;15801	chr2:178733815;178733814;178733813	chr2:179598542;179598541;179598540
N2AB	4875	14848;14849;14850	chr2:178733815;178733814;178733813	chr2:179598542;179598541;179598540
N2A	3948	12067;12068;12069	chr2:178733815;178733814;178733813	chr2:179598542;179598541;179598540
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-35
• Domain position: 25
• Structural Position: 38
• Q(SASA): 0.7702
• 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/K	None	None	0.001	N	0.119	0.131	0.181679512989	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.625E-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	0.2546	likely_benign	0.2651	benign	-0.041	Destabilizing	0.25	N	0.333	neutral	None	None	None	None	I
R/C	0.1849	likely_benign	0.2055	benign	-0.27	Destabilizing	0.992	D	0.307	neutral	None	None	None	None	I
R/D	0.5912	likely_pathogenic	0.6065	pathogenic	-0.156	Destabilizing	0.617	D	0.387	neutral	None	None	None	None	I
R/E	0.2849	likely_benign	0.2767	benign	-0.114	Destabilizing	0.25	N	0.307	neutral	None	None	None	None	I
R/F	0.4414	ambiguous	0.4701	ambiguous	-0.358	Destabilizing	0.972	D	0.324	neutral	None	None	None	None	I
R/G	0.1941	likely_benign	0.2067	benign	-0.191	Destabilizing	0.549	D	0.37	neutral	N	0.48610521	None	None	I
R/H	0.0996	likely_benign	0.099	benign	-0.608	Destabilizing	0.92	D	0.38	neutral	None	None	None	None	I
R/I	0.2227	likely_benign	0.2322	benign	0.31	Stabilizing	0.896	D	0.354	neutral	N	0.494782061	None	None	I
R/K	0.0753	likely_benign	0.0773	benign	-0.147	Destabilizing	0.001	N	0.119	neutral	N	0.367531515	None	None	I
R/L	0.2039	likely_benign	0.218	benign	0.31	Stabilizing	0.617	D	0.37	neutral	None	None	None	None	I
R/M	0.2111	likely_benign	0.2138	benign	-0.052	Destabilizing	0.972	D	0.351	neutral	None	None	None	None	I
R/N	0.4368	ambiguous	0.4427	ambiguous	0.002	Stabilizing	0.617	D	0.312	neutral	None	None	None	None	I
R/P	0.8822	likely_pathogenic	0.9112	pathogenic	0.212	Stabilizing	0.766	D	0.381	neutral	None	None	None	None	I
R/Q	0.0945	likely_benign	0.0941	benign	-0.09	Destabilizing	0.447	N	0.323	neutral	None	None	None	None	I
R/S	0.3057	likely_benign	0.3065	benign	-0.298	Destabilizing	0.201	N	0.342	neutral	N	0.43847237	None	None	I
R/T	0.1574	likely_benign	0.1486	benign	-0.141	Destabilizing	0.549	D	0.379	neutral	N	0.367878309	None	None	I
R/V	0.2749	likely_benign	0.2884	benign	0.212	Stabilizing	0.617	D	0.395	neutral	None	None	None	None	I
R/W	0.1883	likely_benign	0.1946	benign	-0.474	Destabilizing	0.992	D	0.331	neutral	None	None	None	None	I
R/Y	0.3459	ambiguous	0.3784	ambiguous	-0.061	Destabilizing	0.972	D	0.355	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.