TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5147	15664;15665;15666	chr2:178734385;178734384;178734383	chr2:179599112;179599111;179599110
N2AB	4830	14713;14714;14715	chr2:178734385;178734384;178734383	chr2:179599112;179599111;179599110
N2A	3903	11932;11933;11934	chr2:178734385;178734384;178734383	chr2:179599112;179599111;179599110
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-34
• Domain position: 73
• Structural Position: 156
• Q(SASA): 0.0601
• Site annotation: disulfide
• 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	rs1159353292	-1.408	0.999	D	0.855	0.751	0.878624890865	gnomAD-2.1.1	4.03E-06	None	None	disulfide	None	N	None	0	0	None	0	0	None	3.28E-05	None	0	0	0
C/Y	rs1159353292	-1.408	0.999	D	0.855	0.751	0.878624890865	gnomAD-4.0.0	1.5943E-06	None	None	disulfide	None	N	None	0	0	None	0	0	None	0	0	0	1.4367E-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	0.8356	likely_pathogenic	0.8939	pathogenic	-1.38	Destabilizing	0.964	D	0.675	prob.neutral	None	None	disulfide	None	N
C/D	0.9994	likely_pathogenic	0.9996	pathogenic	-1.531	Destabilizing	0.999	D	0.87	deleterious	None	None	disulfide	None	N
C/E	0.9996	likely_pathogenic	0.9997	pathogenic	-1.272	Destabilizing	0.999	D	0.869	deleterious	None	None	disulfide	None	N
C/F	0.7948	likely_pathogenic	0.8413	pathogenic	-0.763	Destabilizing	0.994	D	0.853	deleterious	D	0.80542453	disulfide	None	N
C/G	0.7763	likely_pathogenic	0.8693	pathogenic	-1.755	Destabilizing	0.997	D	0.855	deleterious	D	0.835407336	disulfide	None	N
C/H	0.9976	likely_pathogenic	0.9986	pathogenic	-1.87	Destabilizing	1.0	D	0.866	deleterious	None	None	disulfide	None	N
C/I	0.7985	likely_pathogenic	0.8444	pathogenic	-0.357	Destabilizing	0.971	D	0.786	deleterious	None	None	disulfide	None	N
C/K	0.9997	likely_pathogenic	0.9997	pathogenic	-0.916	Destabilizing	0.998	D	0.861	deleterious	None	None	disulfide	None	N
C/L	0.7364	likely_pathogenic	0.7712	pathogenic	-0.357	Destabilizing	0.931	D	0.747	deleterious	None	None	disulfide	None	N
C/M	0.898	likely_pathogenic	0.92	pathogenic	0.377	Stabilizing	0.931	D	0.611	neutral	None	None	disulfide	None	N
C/N	0.9953	likely_pathogenic	0.9973	pathogenic	-1.727	Destabilizing	0.999	D	0.87	deleterious	None	None	disulfide	None	N
C/P	0.999	likely_pathogenic	0.9994	pathogenic	-0.676	Destabilizing	0.999	D	0.867	deleterious	None	None	disulfide	None	N
C/Q	0.9988	likely_pathogenic	0.9992	pathogenic	-1.203	Destabilizing	0.998	D	0.869	deleterious	None	None	disulfide	None	N
C/R	0.9964	likely_pathogenic	0.9974	pathogenic	-1.364	Destabilizing	0.997	D	0.867	deleterious	D	0.835407336	disulfide	None	N
C/S	0.9621	likely_pathogenic	0.9812	pathogenic	-1.974	Destabilizing	0.99	D	0.77	deleterious	D	0.783409376	disulfide	None	N
C/T	0.9581	likely_pathogenic	0.9743	pathogenic	-1.522	Destabilizing	0.993	D	0.787	deleterious	None	None	disulfide	None	N
C/V	0.6717	likely_pathogenic	0.7376	pathogenic	-0.676	Destabilizing	0.971	D	0.763	deleterious	None	None	disulfide	None	N
C/W	0.9878	likely_pathogenic	0.9924	pathogenic	-1.182	Destabilizing	1.0	D	0.849	deleterious	D	0.835407336	disulfide	None	N
C/Y	0.9614	likely_pathogenic	0.9761	pathogenic	-0.948	Destabilizing	0.999	D	0.855	deleterious	D	0.836314793	disulfide	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.