TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15551	46876;46877;46878	chr2:178619666;178619665;178619664	chr2:179484393;179484392;179484391
N2AB	13910	41953;41954;41955	chr2:178619666;178619665;178619664	chr2:179484393;179484392;179484391
N2A	12983	39172;39173;39174	chr2:178619666;178619665;178619664	chr2:179484393;179484392;179484391
N2B	6486	19681;19682;19683	chr2:178619666;178619665;178619664	chr2:179484393;179484392;179484391
Novex-1	6611	20056;20057;20058	chr2:178619666;178619665;178619664	chr2:179484393;179484392;179484391
Novex-2	6678	20257;20258;20259	chr2:178619666;178619665;178619664	chr2:179484393;179484392;179484391
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Ig-107
• Domain position: 72
• Structural Position: 156
• Q(SASA): 0.0682
• 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/L	None	None	0.015	N	0.37	0.344	0.411665641125	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
F/Y	rs1329504399	-1.403	0.986	D	0.619	0.521	0.652270480338	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.93E-06	0
F/Y	rs1329504399	-1.403	0.986	D	0.619	0.521	0.652270480338	gnomAD-4.0.0	1.59486E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86503E-06	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
F/A	0.9861	likely_pathogenic	0.9809	pathogenic	-2.849	Highly Destabilizing	0.863	D	0.709	prob.delet.	None	None	None	None	N
F/C	0.8314	likely_pathogenic	0.8057	pathogenic	-1.627	Destabilizing	0.999	D	0.807	deleterious	N	0.409342032	None	None	N
F/D	0.9996	likely_pathogenic	0.9995	pathogenic	-3.671	Highly Destabilizing	0.997	D	0.811	deleterious	None	None	None	None	N
F/E	0.9993	likely_pathogenic	0.999	pathogenic	-3.457	Highly Destabilizing	0.997	D	0.803	deleterious	None	None	None	None	N
F/G	0.9961	likely_pathogenic	0.995	pathogenic	-3.269	Highly Destabilizing	0.99	D	0.786	deleterious	None	None	None	None	N
F/H	0.9957	likely_pathogenic	0.9946	pathogenic	-1.994	Destabilizing	0.999	D	0.751	deleterious	None	None	None	None	N
F/I	0.529	ambiguous	0.4764	ambiguous	-1.451	Destabilizing	0.061	N	0.409	neutral	N	0.424532594	None	None	N
F/K	0.9992	likely_pathogenic	0.9987	pathogenic	-2.192	Highly Destabilizing	0.997	D	0.802	deleterious	None	None	None	None	N
F/L	0.9318	likely_pathogenic	0.9236	pathogenic	-1.451	Destabilizing	0.015	N	0.37	neutral	N	0.514838817	None	None	N
F/M	0.8162	likely_pathogenic	0.771	pathogenic	-1.066	Destabilizing	0.982	D	0.679	prob.neutral	None	None	None	None	N
F/N	0.9981	likely_pathogenic	0.9973	pathogenic	-2.796	Highly Destabilizing	0.997	D	0.824	deleterious	None	None	None	None	N
F/P	0.9998	likely_pathogenic	0.9997	pathogenic	-1.933	Destabilizing	0.997	D	0.824	deleterious	None	None	None	None	N
F/Q	0.9983	likely_pathogenic	0.9975	pathogenic	-2.714	Highly Destabilizing	0.997	D	0.825	deleterious	None	None	None	None	N
F/R	0.9971	likely_pathogenic	0.9962	pathogenic	-1.828	Destabilizing	0.997	D	0.822	deleterious	None	None	None	None	N
F/S	0.9967	likely_pathogenic	0.9959	pathogenic	-3.269	Highly Destabilizing	0.959	D	0.754	deleterious	D	0.541157292	None	None	N
F/T	0.9957	likely_pathogenic	0.9932	pathogenic	-2.947	Highly Destabilizing	0.939	D	0.74	deleterious	None	None	None	None	N
F/V	0.6027	likely_pathogenic	0.5827	pathogenic	-1.933	Destabilizing	0.061	N	0.539	neutral	N	0.505016019	None	None	N
F/W	0.9473	likely_pathogenic	0.9463	pathogenic	-0.606	Destabilizing	0.999	D	0.651	neutral	None	None	None	None	N
F/Y	0.6991	likely_pathogenic	0.7091	pathogenic	-1.013	Destabilizing	0.986	D	0.619	neutral	D	0.541157292	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.