TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16173	48742;48743;48744	chr2:178615428;178615427;178615426	chr2:179480155;179480154;179480153
N2AB	14532	43819;43820;43821	chr2:178615428;178615427;178615426	chr2:179480155;179480154;179480153
N2A	13605	41038;41039;41040	chr2:178615428;178615427;178615426	chr2:179480155;179480154;179480153
N2B	7108	21547;21548;21549	chr2:178615428;178615427;178615426	chr2:179480155;179480154;179480153
Novex-1	7233	21922;21923;21924	chr2:178615428;178615427;178615426	chr2:179480155;179480154;179480153
Novex-2	7300	22123;22124;22125	chr2:178615428;178615427;178615426	chr2:179480155;179480154;179480153
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: Fn3-5
• Domain position: 19
• Structural Position: 21
• Q(SASA): 0.1413
• 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	0.999	N	0.512	0.436	0.431712495121	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/S	rs1576472588	None	1.0	N	0.766	0.48	0.744465519958	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

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	0.7129	likely_pathogenic	0.7947	pathogenic	-2.713	Highly Destabilizing	1.0	D	0.708	prob.delet.	None	None	None	None	N
F/C	0.481	ambiguous	0.5767	pathogenic	-1.416	Destabilizing	1.0	D	0.825	deleterious	N	0.478657193	None	None	N
F/D	0.9186	likely_pathogenic	0.9466	pathogenic	-1.857	Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
F/E	0.9154	likely_pathogenic	0.9438	pathogenic	-1.76	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
F/G	0.8937	likely_pathogenic	0.9251	pathogenic	-3.062	Highly Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
F/H	0.5591	ambiguous	0.6423	pathogenic	-1.237	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
F/I	0.3511	ambiguous	0.4368	ambiguous	-1.633	Destabilizing	1.0	D	0.653	neutral	N	0.44269466	None	None	N
F/K	0.8811	likely_pathogenic	0.9212	pathogenic	-1.487	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
F/L	0.8608	likely_pathogenic	0.8961	pathogenic	-1.633	Destabilizing	0.999	D	0.512	neutral	N	0.428616841	None	None	N
F/M	0.6302	likely_pathogenic	0.7136	pathogenic	-1.264	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
F/N	0.7448	likely_pathogenic	0.8153	pathogenic	-1.522	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
F/P	0.9958	likely_pathogenic	0.9977	pathogenic	-1.992	Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
F/Q	0.8144	likely_pathogenic	0.8696	pathogenic	-1.684	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
F/R	0.7954	likely_pathogenic	0.8442	pathogenic	-0.705	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
F/S	0.4979	ambiguous	0.5956	pathogenic	-2.316	Highly Destabilizing	1.0	D	0.766	deleterious	N	0.443893568	None	None	N
F/T	0.5229	ambiguous	0.6211	pathogenic	-2.13	Highly Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
F/V	0.3311	likely_benign	0.417	ambiguous	-1.992	Destabilizing	1.0	D	0.683	prob.neutral	N	0.441413655	None	None	N
F/W	0.613	likely_pathogenic	0.6738	pathogenic	-0.59	Destabilizing	1.0	D	0.686	prob.neutral	None	None	None	None	N
F/Y	0.1898	likely_benign	0.2119	benign	-0.856	Destabilizing	0.999	D	0.455	neutral	N	0.47559197	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.