TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7156	21691;21692;21693	chr2:178723634;178723633;178723632	chr2:179588361;179588360;179588359
N2AB	6839	20740;20741;20742	chr2:178723634;178723633;178723632	chr2:179588361;179588360;179588359
N2A	5912	17959;17960;17961	chr2:178723634;178723633;178723632	chr2:179588361;179588360;179588359
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: F
• RefSeq wild type transcript codon: TTC
• RefSeq wild type template codon: AAG
• Domain: Ig-56
• Domain position: 20
• Structural Position: 30
• Q(SASA): 0.1074
• 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
F/Y	None	None	0.026	D	0.307	0.613	0.644949520829	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-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
F/A	0.9655	likely_pathogenic	0.9658	pathogenic	-2.45	Highly Destabilizing	0.919	D	0.781	deleterious	None	None	None	None	N
F/C	0.8546	likely_pathogenic	0.8545	pathogenic	-1.615	Destabilizing	0.999	D	0.856	deleterious	D	0.627040578	None	None	N
F/D	0.9979	likely_pathogenic	0.9981	pathogenic	-3.382	Highly Destabilizing	0.996	D	0.882	deleterious	None	None	None	None	N
F/E	0.9971	likely_pathogenic	0.9972	pathogenic	-3.12	Highly Destabilizing	0.988	D	0.884	deleterious	None	None	None	None	N
F/G	0.9899	likely_pathogenic	0.9904	pathogenic	-2.935	Highly Destabilizing	0.988	D	0.849	deleterious	None	None	None	None	N
F/H	0.9799	likely_pathogenic	0.9822	pathogenic	-2.203	Highly Destabilizing	0.976	D	0.764	deleterious	None	None	None	None	N
F/I	0.5495	ambiguous	0.5255	ambiguous	-0.844	Destabilizing	0.811	D	0.671	neutral	N	0.50292639	None	None	N
F/K	0.9966	likely_pathogenic	0.9969	pathogenic	-2.173	Highly Destabilizing	0.988	D	0.883	deleterious	None	None	None	None	N
F/L	0.8642	likely_pathogenic	0.8481	pathogenic	-0.844	Destabilizing	0.026	N	0.323	neutral	N	0.479646347	None	None	N
F/M	0.7503	likely_pathogenic	0.7257	pathogenic	-0.738	Destabilizing	0.976	D	0.687	prob.neutral	None	None	None	None	N
F/N	0.9907	likely_pathogenic	0.9917	pathogenic	-2.907	Highly Destabilizing	0.988	D	0.874	deleterious	None	None	None	None	N
F/P	0.9995	likely_pathogenic	0.9994	pathogenic	-1.396	Destabilizing	0.996	D	0.885	deleterious	None	None	None	None	N
F/Q	0.9939	likely_pathogenic	0.9942	pathogenic	-2.617	Highly Destabilizing	0.988	D	0.88	deleterious	None	None	None	None	N
F/R	0.9905	likely_pathogenic	0.9915	pathogenic	-2.196	Highly Destabilizing	0.988	D	0.883	deleterious	None	None	None	None	N
F/S	0.9735	likely_pathogenic	0.9761	pathogenic	-3.341	Highly Destabilizing	0.984	D	0.836	deleterious	D	0.627040578	None	None	N
F/T	0.9826	likely_pathogenic	0.9824	pathogenic	-2.941	Highly Destabilizing	0.988	D	0.837	deleterious	None	None	None	None	N
F/V	0.5974	likely_pathogenic	0.5786	pathogenic	-1.396	Destabilizing	0.811	D	0.701	prob.neutral	D	0.526488374	None	None	N
F/W	0.8784	likely_pathogenic	0.8803	pathogenic	-0.3	Destabilizing	0.997	D	0.683	prob.neutral	None	None	None	None	N
F/Y	0.5297	ambiguous	0.5607	ambiguous	-0.737	Destabilizing	0.026	N	0.307	neutral	D	0.594800052	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.