TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13907	41944;41945;41946	chr2:178635605;178635604;178635603	chr2:179500332;179500331;179500330
N2AB	12266	37021;37022;37023	chr2:178635605;178635604;178635603	chr2:179500332;179500331;179500330
N2A	11339	34240;34241;34242	chr2:178635605;178635604;178635603	chr2:179500332;179500331;179500330
N2B	4842	14749;14750;14751	chr2:178635605;178635604;178635603	chr2:179500332;179500331;179500330
Novex-1	4967	15124;15125;15126	chr2:178635605;178635604;178635603	chr2:179500332;179500331;179500330
Novex-2	5034	15325;15326;15327	chr2:178635605;178635604;178635603	chr2:179500332;179500331;179500330
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-89
• Domain position: 32
• Structural Position: 49
• Q(SASA): 0.1309
• 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	rs1192032110	None	None	N	0.227	0.116	0.292787519742	gnomAD-4.0.0	2.08134E-06	None	None	None	None	N	None	0	2.40941E-05	None	0	0	None	0	0	9.08447E-07	0	1.67577E-05

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	0.9889	likely_pathogenic	0.9856	pathogenic	-3.299	Highly Destabilizing	0.147	N	0.693	prob.delet.	None	None	None	None	N
F/C	0.9224	likely_pathogenic	0.8832	pathogenic	-1.864	Destabilizing	0.914	D	0.791	deleterious	N	0.448526661	None	None	N
F/D	0.997	likely_pathogenic	0.996	pathogenic	-3.326	Highly Destabilizing	0.552	D	0.83	deleterious	None	None	None	None	N
F/E	0.9955	likely_pathogenic	0.9943	pathogenic	-3.186	Highly Destabilizing	0.552	D	0.811	deleterious	None	None	None	None	N
F/G	0.9934	likely_pathogenic	0.9916	pathogenic	-3.653	Highly Destabilizing	0.552	D	0.743	deleterious	None	None	None	None	N
F/H	0.9064	likely_pathogenic	0.8869	pathogenic	-1.912	Destabilizing	0.378	N	0.676	prob.neutral	None	None	None	None	N
F/I	0.8951	likely_pathogenic	0.8564	pathogenic	-2.145	Highly Destabilizing	0.061	N	0.556	neutral	N	0.443133345	None	None	N
F/K	0.9915	likely_pathogenic	0.9889	pathogenic	-2.127	Highly Destabilizing	0.378	N	0.787	deleterious	None	None	None	None	N
F/L	0.9825	likely_pathogenic	0.9714	pathogenic	-2.145	Highly Destabilizing	None	N	0.227	neutral	N	0.445633119	None	None	N
F/M	0.9335	likely_pathogenic	0.9074	pathogenic	-1.764	Destabilizing	0.378	N	0.593	neutral	None	None	None	None	N
F/N	0.979	likely_pathogenic	0.9743	pathogenic	-2.366	Highly Destabilizing	0.552	D	0.823	deleterious	None	None	None	None	N
F/P	0.9999	likely_pathogenic	0.9999	pathogenic	-2.539	Highly Destabilizing	0.789	D	0.818	deleterious	None	None	None	None	N
F/Q	0.9822	likely_pathogenic	0.9768	pathogenic	-2.498	Highly Destabilizing	0.552	D	0.82	deleterious	None	None	None	None	N
F/R	0.9767	likely_pathogenic	0.9714	pathogenic	-1.321	Destabilizing	0.378	N	0.828	deleterious	None	None	None	None	N
F/S	0.9787	likely_pathogenic	0.9732	pathogenic	-2.994	Highly Destabilizing	0.314	N	0.728	deleterious	N	0.483875122	None	None	N
F/T	0.9869	likely_pathogenic	0.9827	pathogenic	-2.77	Highly Destabilizing	0.378	N	0.736	deleterious	None	None	None	None	N
F/V	0.8893	likely_pathogenic	0.8518	pathogenic	-2.539	Highly Destabilizing	0.061	N	0.653	prob.neutral	N	0.483651669	None	None	N
F/W	0.6944	likely_pathogenic	0.6362	pathogenic	-0.869	Destabilizing	0.823	D	0.615	neutral	None	None	None	None	N
F/Y	0.1853	likely_benign	0.1736	benign	-1.26	Destabilizing	None	N	0.312	neutral	N	0.434561967	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.