TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6468	19627;19628;19629	chr2:178728524;178728523;178728522	chr2:179593251;179593250;179593249
N2AB	6151	18676;18677;18678	chr2:178728524;178728523;178728522	chr2:179593251;179593250;179593249
N2A	5224	15895;15896;15897	chr2:178728524;178728523;178728522	chr2:179593251;179593250;179593249
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: C
• RefSeq wild type transcript codon: TGT
• RefSeq wild type template codon: ACA
• Domain: Ig-48
• Domain position: 84
• Structural Position: 169
• Q(SASA): 0.1312
• 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/S	rs776818687	-1.571	1.0	N	0.811	0.538	0.728107646935	gnomAD-2.1.1	4.05E-06	None	None	None	None	N	None	0	2.92E-05	None	0	0	None	0	None	0	0	0
C/S	rs776818687	-1.571	1.0	N	0.811	0.538	0.728107646935	gnomAD-4.0.0	3.19324E-06	None	None	None	None	N	None	0	2.29589E-05	None	0	0	None	0	0	0	1.43823E-05	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	0.5697	likely_pathogenic	0.6207	pathogenic	-1.868	Destabilizing	0.998	D	0.601	neutral	None	None	None	None	N
C/D	0.8757	likely_pathogenic	0.9049	pathogenic	-0.361	Destabilizing	1.0	D	0.914	deleterious	None	None	None	None	N
C/E	0.9356	likely_pathogenic	0.9532	pathogenic	-0.25	Destabilizing	1.0	D	0.926	deleterious	None	None	None	None	N
C/F	0.4488	ambiguous	0.5374	ambiguous	-1.27	Destabilizing	1.0	D	0.923	deleterious	N	0.512786714	None	None	N
C/G	0.3638	ambiguous	0.3755	ambiguous	-2.181	Highly Destabilizing	1.0	D	0.865	deleterious	N	0.503076249	None	None	N
C/H	0.8259	likely_pathogenic	0.8622	pathogenic	-2.166	Highly Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	N
C/I	0.7747	likely_pathogenic	0.8212	pathogenic	-1.058	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
C/K	0.9529	likely_pathogenic	0.9673	pathogenic	-0.912	Destabilizing	1.0	D	0.91	deleterious	None	None	None	None	N
C/L	0.7612	likely_pathogenic	0.808	pathogenic	-1.058	Destabilizing	0.999	D	0.659	neutral	None	None	None	None	N
C/M	0.8029	likely_pathogenic	0.8526	pathogenic	-0.136	Destabilizing	1.0	D	0.872	deleterious	None	None	None	None	N
C/N	0.8139	likely_pathogenic	0.8469	pathogenic	-0.938	Destabilizing	1.0	D	0.926	deleterious	None	None	None	None	N
C/P	0.9967	likely_pathogenic	0.9966	pathogenic	-1.303	Destabilizing	1.0	D	0.925	deleterious	None	None	None	None	N
C/Q	0.856	likely_pathogenic	0.8909	pathogenic	-0.83	Destabilizing	1.0	D	0.919	deleterious	None	None	None	None	N
C/R	0.7708	likely_pathogenic	0.8132	pathogenic	-0.827	Destabilizing	1.0	D	0.926	deleterious	N	0.488326129	None	None	N
C/S	0.37	ambiguous	0.3975	ambiguous	-1.503	Destabilizing	1.0	D	0.811	deleterious	N	0.510006539	None	None	N
C/T	0.5488	ambiguous	0.6041	pathogenic	-1.199	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
C/V	0.636	likely_pathogenic	0.701	pathogenic	-1.303	Destabilizing	0.999	D	0.723	prob.delet.	None	None	None	None	N
C/W	0.7955	likely_pathogenic	0.8401	pathogenic	-1.236	Destabilizing	1.0	D	0.906	deleterious	N	0.521940973	None	None	N
C/Y	0.6924	likely_pathogenic	0.7571	pathogenic	-1.224	Destabilizing	1.0	D	0.924	deleterious	N	0.516661054	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.