TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33351	100276;100277;100278	chr2:178537058;178537057;178537056	chr2:179401785;179401784;179401783
N2AB	31710	95353;95354;95355	chr2:178537058;178537057;178537056	chr2:179401785;179401784;179401783
N2A	30783	92572;92573;92574	chr2:178537058;178537057;178537056	chr2:179401785;179401784;179401783
N2B	24286	73081;73082;73083	chr2:178537058;178537057;178537056	chr2:179401785;179401784;179401783
Novex-1	24411	73456;73457;73458	chr2:178537058;178537057;178537056	chr2:179401785;179401784;179401783
Novex-2	24478	73657;73658;73659	chr2:178537058;178537057;178537056	chr2:179401785;179401784;179401783
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGT
• RefSeq wild type template codon: ACA
• Domain: Fn3-130
• Domain position: 62
• Structural Position: 91
• Q(SASA): 0.1199
• 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
C/Y	None	None	0.999	N	0.726	0.425	0.662473173981	gnomAD-4.0.0	1.59303E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86067E-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
C/A	0.7565	likely_pathogenic	0.7849	pathogenic	-1.269	Destabilizing	0.964	D	0.576	neutral	None	None	None	None	N
C/D	0.9925	likely_pathogenic	0.9954	pathogenic	0.186	Stabilizing	0.999	D	0.781	deleterious	None	None	None	None	N
C/E	0.9928	likely_pathogenic	0.9963	pathogenic	0.329	Stabilizing	0.999	D	0.786	deleterious	None	None	None	None	N
C/F	0.55	ambiguous	0.6469	pathogenic	-0.768	Destabilizing	0.997	D	0.696	prob.neutral	N	0.442903608	None	None	N
C/G	0.6623	likely_pathogenic	0.7063	pathogenic	-1.577	Destabilizing	0.999	D	0.739	prob.delet.	N	0.495309163	None	None	N
C/H	0.9421	likely_pathogenic	0.9645	pathogenic	-1.471	Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
C/I	0.8453	likely_pathogenic	0.8848	pathogenic	-0.476	Destabilizing	0.971	D	0.604	neutral	None	None	None	None	N
C/K	0.9934	likely_pathogenic	0.997	pathogenic	-0.286	Destabilizing	0.999	D	0.771	deleterious	None	None	None	None	N
C/L	0.7585	likely_pathogenic	0.8343	pathogenic	-0.476	Destabilizing	0.931	D	0.619	neutral	None	None	None	None	N
C/M	0.8725	likely_pathogenic	0.9109	pathogenic	0.279	Stabilizing	0.998	D	0.672	neutral	None	None	None	None	N
C/N	0.9574	likely_pathogenic	0.9691	pathogenic	-0.635	Destabilizing	0.999	D	0.814	deleterious	None	None	None	None	N
C/P	0.998	likely_pathogenic	0.9986	pathogenic	-0.714	Destabilizing	0.999	D	0.794	deleterious	None	None	None	None	N
C/Q	0.9693	likely_pathogenic	0.9819	pathogenic	-0.353	Destabilizing	0.999	D	0.811	deleterious	None	None	None	None	N
C/R	0.9571	likely_pathogenic	0.9766	pathogenic	-0.385	Destabilizing	0.999	D	0.815	deleterious	N	0.501892529	None	None	N
C/S	0.7557	likely_pathogenic	0.7688	pathogenic	-1.12	Destabilizing	0.99	D	0.644	neutral	N	0.483534784	None	None	N
C/T	0.8481	likely_pathogenic	0.8735	pathogenic	-0.775	Destabilizing	0.985	D	0.634	neutral	None	None	None	None	N
C/V	0.7327	likely_pathogenic	0.7772	pathogenic	-0.714	Destabilizing	0.469	N	0.502	neutral	None	None	None	None	N
C/W	0.9158	likely_pathogenic	0.9458	pathogenic	-0.847	Destabilizing	1.0	D	0.727	prob.delet.	N	0.483788274	None	None	N
C/Y	0.7296	likely_pathogenic	0.8164	pathogenic	-0.734	Destabilizing	0.999	D	0.726	prob.delet.	N	0.472626295	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.