TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15126	45601;45602;45603	chr2:178621342;178621341;178621340	chr2:179486069;179486068;179486067
N2AB	13485	40678;40679;40680	chr2:178621342;178621341;178621340	chr2:179486069;179486068;179486067
N2A	12558	37897;37898;37899	chr2:178621342;178621341;178621340	chr2:179486069;179486068;179486067
N2B	6061	18406;18407;18408	chr2:178621342;178621341;178621340	chr2:179486069;179486068;179486067
Novex-1	6186	18781;18782;18783	chr2:178621342;178621341;178621340	chr2:179486069;179486068;179486067
Novex-2	6253	18982;18983;18984	chr2:178621342;178621341;178621340	chr2:179486069;179486068;179486067
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: Ig-103
• Domain position: 7
• Structural Position: 8
• Q(SASA): 0.2123
• 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/A	rs2058234683	None	0.998	D	0.625	0.45	0.365120060079	gnomAD-4.0.0	1.43693E-05	None	None	None	None	N	None	0	0	None	0	2.51411E-04	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
P/A	0.8549	likely_pathogenic	0.8475	pathogenic	-1.544	Destabilizing	0.998	D	0.625	neutral	D	0.559853642	None	None	N
P/C	0.9943	likely_pathogenic	0.9934	pathogenic	-0.977	Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
P/D	0.999	likely_pathogenic	0.9988	pathogenic	-1.739	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
P/E	0.9973	likely_pathogenic	0.9967	pathogenic	-1.508	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
P/F	0.9975	likely_pathogenic	0.9974	pathogenic	-0.805	Destabilizing	1.0	D	0.898	deleterious	None	None	None	None	N
P/G	0.9861	likely_pathogenic	0.9862	pathogenic	-2.094	Highly Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
P/H	0.9971	likely_pathogenic	0.996	pathogenic	-1.888	Destabilizing	1.0	D	0.873	deleterious	D	0.679968572	None	None	N
P/I	0.9505	likely_pathogenic	0.9549	pathogenic	-0.017	Destabilizing	0.998	D	0.854	deleterious	None	None	None	None	N
P/K	0.9985	likely_pathogenic	0.998	pathogenic	-1.033	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	N
P/L	0.7949	likely_pathogenic	0.8277	pathogenic	-0.017	Destabilizing	0.64	D	0.579	neutral	N	0.44240773	None	None	N
P/M	0.9718	likely_pathogenic	0.9766	pathogenic	-0.11	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
P/N	0.9979	likely_pathogenic	0.9978	pathogenic	-1.326	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
P/Q	0.9944	likely_pathogenic	0.9933	pathogenic	-1.121	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
P/R	0.9962	likely_pathogenic	0.9949	pathogenic	-1.083	Destabilizing	1.0	D	0.868	deleterious	D	0.640248546	None	None	N
P/S	0.9886	likely_pathogenic	0.9856	pathogenic	-1.992	Destabilizing	1.0	D	0.768	deleterious	D	0.616410793	None	None	N
P/T	0.9576	likely_pathogenic	0.9574	pathogenic	-1.602	Destabilizing	0.999	D	0.764	deleterious	D	0.638942205	None	None	N
P/V	0.9182	likely_pathogenic	0.9194	pathogenic	-0.497	Destabilizing	0.998	D	0.754	deleterious	None	None	None	None	N
P/W	0.9997	likely_pathogenic	0.9996	pathogenic	-1.296	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
P/Y	0.9991	likely_pathogenic	0.9989	pathogenic	-0.837	Destabilizing	1.0	D	0.896	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.