TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16912	50959;50960;50961	chr2:178611495;178611494;178611493	chr2:179476222;179476221;179476220
N2AB	15271	46036;46037;46038	chr2:178611495;178611494;178611493	chr2:179476222;179476221;179476220
N2A	14344	43255;43256;43257	chr2:178611495;178611494;178611493	chr2:179476222;179476221;179476220
N2B	7847	23764;23765;23766	chr2:178611495;178611494;178611493	chr2:179476222;179476221;179476220
Novex-1	7972	24139;24140;24141	chr2:178611495;178611494;178611493	chr2:179476222;179476221;179476220
Novex-2	8039	24340;24341;24342	chr2:178611495;178611494;178611493	chr2:179476222;179476221;179476220
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: Fn3-11
• Domain position: 61
• Structural Position: 91
• Q(SASA): 0.1581
• 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/C	rs2056317849	None	0.009	N	0.491	0.257	0.455722563999	gnomAD-4.0.0	3.42256E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.5991E-06	0	1.65777E-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	0.8429	likely_pathogenic	0.914	pathogenic	-2.32	Highly Destabilizing	0.25	N	0.511	neutral	None	None	None	None	N
F/C	0.3523	ambiguous	0.4639	ambiguous	-1.719	Destabilizing	0.009	N	0.491	neutral	N	0.484001765	None	None	N
F/D	0.959	likely_pathogenic	0.9849	pathogenic	-2.29	Highly Destabilizing	0.972	D	0.626	neutral	None	None	None	None	N
F/E	0.9614	likely_pathogenic	0.9837	pathogenic	-2.114	Highly Destabilizing	0.92	D	0.618	neutral	None	None	None	None	N
F/G	0.8674	likely_pathogenic	0.9419	pathogenic	-2.706	Highly Destabilizing	0.766	D	0.578	neutral	None	None	None	None	N
F/H	0.7163	likely_pathogenic	0.8271	pathogenic	-1.078	Destabilizing	0.85	D	0.513	neutral	None	None	None	None	N
F/I	0.6091	likely_pathogenic	0.685	pathogenic	-1.095	Destabilizing	0.549	D	0.407	neutral	N	0.475175124	None	None	N
F/K	0.9562	likely_pathogenic	0.9798	pathogenic	-2.071	Highly Destabilizing	0.92	D	0.618	neutral	None	None	None	None	N
F/L	0.9329	likely_pathogenic	0.9502	pathogenic	-1.095	Destabilizing	0.201	N	0.426	neutral	N	0.476482206	None	None	N
F/M	0.7555	likely_pathogenic	0.8305	pathogenic	-0.902	Destabilizing	0.972	D	0.414	neutral	None	None	None	None	N
F/N	0.8642	likely_pathogenic	0.9368	pathogenic	-2.54	Highly Destabilizing	0.92	D	0.628	neutral	None	None	None	None	N
F/P	0.998	likely_pathogenic	0.9989	pathogenic	-1.508	Destabilizing	0.972	D	0.651	neutral	None	None	None	None	N
F/Q	0.9185	likely_pathogenic	0.9608	pathogenic	-2.451	Highly Destabilizing	0.92	D	0.654	neutral	None	None	None	None	N
F/R	0.9223	likely_pathogenic	0.9564	pathogenic	-1.616	Destabilizing	0.92	D	0.629	neutral	None	None	None	None	N
F/S	0.8399	likely_pathogenic	0.9104	pathogenic	-3.174	Highly Destabilizing	0.549	D	0.529	neutral	N	0.509573125	None	None	N
F/T	0.8855	likely_pathogenic	0.9431	pathogenic	-2.887	Highly Destabilizing	0.617	D	0.547	neutral	None	None	None	None	N
F/V	0.5542	ambiguous	0.6463	pathogenic	-1.508	Destabilizing	0.549	D	0.462	neutral	N	0.473096063	None	None	N
F/W	0.4989	ambiguous	0.6226	pathogenic	-0.237	Destabilizing	0.92	D	0.425	neutral	None	None	None	None	N
F/Y	0.0897	likely_benign	0.1078	benign	-0.571	Destabilizing	0.001	N	0.145	neutral	N	0.420149073	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.