TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27948	84067;84068;84069	chr2:178562290;178562289;178562288	chr2:179427017;179427016;179427015
N2AB	26307	79144;79145;79146	chr2:178562290;178562289;178562288	chr2:179427017;179427016;179427015
N2A	25380	76363;76364;76365	chr2:178562290;178562289;178562288	chr2:179427017;179427016;179427015
N2B	18883	56872;56873;56874	chr2:178562290;178562289;178562288	chr2:179427017;179427016;179427015
Novex-1	19008	57247;57248;57249	chr2:178562290;178562289;178562288	chr2:179427017;179427016;179427015
Novex-2	19075	57448;57449;57450	chr2:178562290;178562289;178562288	chr2:179427017;179427016;179427015
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: Fn3-91
• Domain position: 86
• Structural Position: 121
• Q(SASA): 0.3818
• 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	None	None	0.904	N	0.491	0.155	0.394079506076	gnomAD-4.0.0	1.59229E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85927E-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	0.6493	likely_pathogenic	0.7775	pathogenic	-0.917	Destabilizing	0.721	D	0.454	neutral	None	None	None	None	I
R/C	0.2353	likely_benign	0.3266	benign	-0.859	Destabilizing	0.999	D	0.617	neutral	None	None	None	None	I
R/D	0.956	likely_pathogenic	0.9777	pathogenic	-0.035	Destabilizing	0.926	D	0.587	neutral	None	None	None	None	I
R/E	0.7416	likely_pathogenic	0.8405	pathogenic	0.13	Stabilizing	0.437	N	0.417	neutral	None	None	None	None	I
R/F	0.8025	likely_pathogenic	0.8942	pathogenic	-0.44	Destabilizing	0.946	D	0.615	neutral	None	None	None	None	I
R/G	0.6096	likely_pathogenic	0.7335	pathogenic	-1.278	Destabilizing	0.904	D	0.559	neutral	N	0.485171518	None	None	I
R/H	0.2419	likely_benign	0.3355	benign	-1.466	Destabilizing	0.991	D	0.545	neutral	None	None	None	None	I
R/I	0.4969	ambiguous	0.678	pathogenic	0.075	Stabilizing	0.662	D	0.556	neutral	N	0.462171164	None	None	I
R/K	0.1712	likely_benign	0.2343	benign	-0.897	Destabilizing	None	N	0.242	neutral	N	0.475917316	None	None	I
R/L	0.5044	ambiguous	0.661	pathogenic	0.075	Stabilizing	0.517	D	0.501	neutral	None	None	None	None	I
R/M	0.5426	ambiguous	0.7038	pathogenic	-0.385	Destabilizing	0.974	D	0.611	neutral	None	None	None	None	I
R/N	0.8868	likely_pathogenic	0.9409	pathogenic	-0.45	Destabilizing	0.926	D	0.42	neutral	None	None	None	None	I
R/P	0.9721	likely_pathogenic	0.9835	pathogenic	-0.235	Destabilizing	0.989	D	0.627	neutral	None	None	None	None	I
R/Q	0.1601	likely_benign	0.2127	benign	-0.489	Destabilizing	0.902	D	0.416	neutral	None	None	None	None	I
R/S	0.7557	likely_pathogenic	0.8514	pathogenic	-1.25	Destabilizing	0.904	D	0.48	neutral	N	0.392844855	None	None	I
R/T	0.5423	ambiguous	0.6971	pathogenic	-0.882	Destabilizing	0.904	D	0.491	neutral	N	0.497887312	None	None	I
R/V	0.5083	ambiguous	0.6778	pathogenic	-0.235	Destabilizing	0.012	N	0.459	neutral	None	None	None	None	I
R/W	0.4744	ambiguous	0.6098	pathogenic	-0.025	Destabilizing	0.999	D	0.644	neutral	None	None	None	None	I
R/Y	0.6859	likely_pathogenic	0.7977	pathogenic	0.211	Stabilizing	0.973	D	0.625	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.