TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19738	59437;59438;59439	chr2:178592907;178592906;178592905	chr2:179457634;179457633;179457632
N2AB	18097	54514;54515;54516	chr2:178592907;178592906;178592905	chr2:179457634;179457633;179457632
N2A	17170	51733;51734;51735	chr2:178592907;178592906;178592905	chr2:179457634;179457633;179457632
N2B	10673	32242;32243;32244	chr2:178592907;178592906;178592905	chr2:179457634;179457633;179457632
Novex-1	10798	32617;32618;32619	chr2:178592907;178592906;178592905	chr2:179457634;179457633;179457632
Novex-2	10865	32818;32819;32820	chr2:178592907;178592906;178592905	chr2:179457634;179457633;179457632
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-31
• Domain position: 59
• Structural Position: 83
• Q(SASA): 0.5177
• 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
P/L	rs879199918	None	0.999	N	0.717	0.404	None	gnomAD-4.0.0	4.77509E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.57814E-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
P/A	0.0892	likely_benign	0.086	benign	-0.919	Destabilizing	0.996	D	0.563	neutral	N	0.49762074	None	None	N
P/C	0.4526	ambiguous	0.4424	ambiguous	-0.757	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
P/D	0.4901	ambiguous	0.477	ambiguous	-0.34	Destabilizing	0.999	D	0.687	prob.neutral	None	None	None	None	N
P/E	0.2565	likely_benign	0.2488	benign	-0.423	Destabilizing	0.994	D	0.6	neutral	None	None	None	None	N
P/F	0.4366	ambiguous	0.4514	ambiguous	-0.951	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
P/G	0.2777	likely_benign	0.2696	benign	-1.116	Destabilizing	1.0	D	0.645	neutral	None	None	None	None	N
P/H	0.1983	likely_benign	0.1984	benign	-0.561	Destabilizing	1.0	D	0.72	prob.delet.	N	0.512051475	None	None	N
P/I	0.2254	likely_benign	0.2262	benign	-0.528	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
P/K	0.1939	likely_benign	0.1946	benign	-0.61	Destabilizing	0.994	D	0.64	neutral	None	None	None	None	N
P/L	0.1044	likely_benign	0.0978	benign	-0.528	Destabilizing	0.999	D	0.717	prob.delet.	N	0.519516165	None	None	N
P/M	0.2456	likely_benign	0.2439	benign	-0.424	Destabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	N
P/N	0.3241	likely_benign	0.319	benign	-0.341	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
P/Q	0.1353	likely_benign	0.1321	benign	-0.586	Destabilizing	0.927	D	0.355	neutral	None	None	None	None	N
P/R	0.1454	likely_benign	0.1436	benign	-0.057	Destabilizing	0.999	D	0.721	prob.delet.	N	0.493310998	None	None	N
P/S	0.1332	likely_benign	0.127	benign	-0.836	Destabilizing	0.999	D	0.666	neutral	N	0.487267673	None	None	N
P/T	0.0954	likely_benign	0.0903	benign	-0.81	Destabilizing	0.999	D	0.696	prob.neutral	N	0.483304649	None	None	N
P/V	0.1628	likely_benign	0.1597	benign	-0.622	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
P/W	0.5693	likely_pathogenic	0.5674	pathogenic	-0.999	Destabilizing	1.0	D	0.744	deleterious	None	None	None	None	N
P/Y	0.4254	ambiguous	0.4297	ambiguous	-0.715	Destabilizing	1.0	D	0.745	deleterious	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.