TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20861	62806;62807;62808	chr2:178589144;178589143;178589142	chr2:179453871;179453870;179453869
N2AB	19220	57883;57884;57885	chr2:178589144;178589143;178589142	chr2:179453871;179453870;179453869
N2A	18293	55102;55103;55104	chr2:178589144;178589143;178589142	chr2:179453871;179453870;179453869
N2B	11796	35611;35612;35613	chr2:178589144;178589143;178589142	chr2:179453871;179453870;179453869
Novex-1	11921	35986;35987;35988	chr2:178589144;178589143;178589142	chr2:179453871;179453870;179453869
Novex-2	11988	36187;36188;36189	chr2:178589144;178589143;178589142	chr2:179453871;179453870;179453869
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-122
• Domain position: 93
• Structural Position: 177
• Q(SASA): 0.5559
• 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
V/A	None	None	0.999	D	0.743	0.806	0.847680696271	gnomAD-4.0.0	1.59262E-06	None	None	None	None	N	None	0	0	None	4.76826E-05	0	None	0	0	0	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
V/A	0.9825	likely_pathogenic	0.982	pathogenic	-1.696	Destabilizing	0.999	D	0.743	deleterious	D	0.627804921	None	None	N
V/C	0.9921	likely_pathogenic	0.9912	pathogenic	-1.516	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
V/D	0.9993	likely_pathogenic	0.9994	pathogenic	-2.145	Highly Destabilizing	1.0	D	0.839	deleterious	D	0.628410334	None	None	N
V/E	0.9979	likely_pathogenic	0.9982	pathogenic	-2.127	Highly Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
V/F	0.9805	likely_pathogenic	0.9814	pathogenic	-1.389	Destabilizing	1.0	D	0.86	deleterious	D	0.60226681	None	None	N
V/G	0.9882	likely_pathogenic	0.9887	pathogenic	-2.017	Highly Destabilizing	1.0	D	0.779	deleterious	D	0.628410334	None	None	N
V/H	0.9994	likely_pathogenic	0.9995	pathogenic	-1.474	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
V/I	0.1249	likely_benign	0.1158	benign	-0.892	Destabilizing	0.997	D	0.713	prob.delet.	N	0.510194545	None	None	N
V/K	0.9984	likely_pathogenic	0.9986	pathogenic	-1.332	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
V/L	0.947	likely_pathogenic	0.9391	pathogenic	-0.892	Destabilizing	0.997	D	0.746	deleterious	D	0.609535353	None	None	N
V/M	0.9549	likely_pathogenic	0.9541	pathogenic	-0.855	Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
V/N	0.9963	likely_pathogenic	0.9961	pathogenic	-1.288	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
V/P	0.9972	likely_pathogenic	0.9967	pathogenic	-1.129	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
V/Q	0.9981	likely_pathogenic	0.9983	pathogenic	-1.503	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
V/R	0.9965	likely_pathogenic	0.9967	pathogenic	-0.824	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
V/S	0.9906	likely_pathogenic	0.991	pathogenic	-1.792	Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	N
V/T	0.9565	likely_pathogenic	0.966	pathogenic	-1.668	Destabilizing	0.999	D	0.797	deleterious	None	None	None	None	N
V/W	0.9998	likely_pathogenic	0.9998	pathogenic	-1.57	Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	N
V/Y	0.9982	likely_pathogenic	0.9982	pathogenic	-1.264	Destabilizing	1.0	D	0.869	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.