TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27515	82768;82769;82770	chr2:178563589;178563588;178563587	chr2:179428316;179428315;179428314
N2AB	25874	77845;77846;77847	chr2:178563589;178563588;178563587	chr2:179428316;179428315;179428314
N2A	24947	75064;75065;75066	chr2:178563589;178563588;178563587	chr2:179428316;179428315;179428314
N2B	18450	55573;55574;55575	chr2:178563589;178563588;178563587	chr2:179428316;179428315;179428314
Novex-1	18575	55948;55949;55950	chr2:178563589;178563588;178563587	chr2:179428316;179428315;179428314
Novex-2	18642	56149;56150;56151	chr2:178563589;178563588;178563587	chr2:179428316;179428315;179428314
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: Fn3-88
• Domain position: 47
• Structural Position: 64
• Q(SASA): 0.8026
• 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	rs757660615	-0.094	1.0	N	0.657	0.426	0.396044805602	gnomAD-2.1.1	1.21E-05	None	None	None	None	I	None	0	0	None	0	5.57E-05	None	0	None	0	1.78E-05	0
R/T	rs757660615	-0.094	1.0	N	0.657	0.426	0.396044805602	gnomAD-4.0.0	7.95651E-06	None	None	None	None	I	None	0	0	None	0	2.77423E-05	None	0	0	1.14337E-05	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	0.8474	likely_pathogenic	0.8222	pathogenic	0.063	Stabilizing	0.999	D	0.643	neutral	None	None	None	None	I
R/C	0.3609	ambiguous	0.3415	ambiguous	-0.305	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	I
R/D	0.9624	likely_pathogenic	0.9555	pathogenic	-0.338	Destabilizing	1.0	D	0.704	prob.neutral	None	None	None	None	I
R/E	0.8759	likely_pathogenic	0.8519	pathogenic	-0.301	Destabilizing	0.999	D	0.687	prob.neutral	None	None	None	None	I
R/F	0.8012	likely_pathogenic	0.7856	pathogenic	-0.289	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	I
R/G	0.683	likely_pathogenic	0.6592	pathogenic	-0.061	Destabilizing	1.0	D	0.619	neutral	N	0.506992372	None	None	I
R/H	0.2149	likely_benign	0.2091	benign	-0.564	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	I
R/I	0.6734	likely_pathogenic	0.6422	pathogenic	0.339	Stabilizing	1.0	D	0.757	deleterious	N	0.48233347	None	None	I
R/K	0.2728	likely_benign	0.2661	benign	-0.195	Destabilizing	0.997	D	0.635	neutral	N	0.5091286	None	None	I
R/L	0.5766	likely_pathogenic	0.55	ambiguous	0.339	Stabilizing	1.0	D	0.619	neutral	None	None	None	None	I
R/M	0.7313	likely_pathogenic	0.6987	pathogenic	-0.134	Destabilizing	1.0	D	0.716	prob.delet.	None	None	None	None	I
R/N	0.9117	likely_pathogenic	0.8927	pathogenic	-0.173	Destabilizing	1.0	D	0.71	prob.delet.	None	None	None	None	I
R/P	0.9293	likely_pathogenic	0.9256	pathogenic	0.264	Stabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	I
R/Q	0.2755	likely_benign	0.2634	benign	-0.173	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	I
R/S	0.8847	likely_pathogenic	0.8685	pathogenic	-0.296	Destabilizing	1.0	D	0.646	neutral	N	0.519497522	None	None	I
R/T	0.7816	likely_pathogenic	0.7402	pathogenic	-0.161	Destabilizing	1.0	D	0.657	neutral	N	0.508744598	None	None	I
R/V	0.7602	likely_pathogenic	0.73	pathogenic	0.264	Stabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	I
R/W	0.3357	likely_benign	0.337	benign	-0.517	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	I
R/Y	0.6283	likely_pathogenic	0.6185	pathogenic	-0.11	Destabilizing	1.0	D	0.723	prob.delet.	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.