TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34260	103003;103004;103005	chr2:178533837;178533836;178533835	chr2:179398564;179398563;179398562
N2AB	32619	98080;98081;98082	chr2:178533837;178533836;178533835	chr2:179398564;179398563;179398562
N2A	31692	95299;95300;95301	chr2:178533837;178533836;178533835	chr2:179398564;179398563;179398562
N2B	25195	75808;75809;75810	chr2:178533837;178533836;178533835	chr2:179398564;179398563;179398562
Novex-1	25320	76183;76184;76185	chr2:178533837;178533836;178533835	chr2:179398564;179398563;179398562
Novex-2	25387	76384;76385;76386	chr2:178533837;178533836;178533835	chr2:179398564;179398563;179398562
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-161
• Domain position: 3
• Structural Position: 3
• Q(SASA): 0.1575
• 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	rs767251580	None	0.76	N	0.627	0.659	0.438593652726	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
F/L	rs767251580	None	0.76	N	0.627	0.659	0.438593652726	gnomAD-4.0.0	6.56978E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.46998E-05	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	0.9975	likely_pathogenic	0.9978	pathogenic	-2.877	Highly Destabilizing	0.953	D	0.783	deleterious	None	None	None	None	N
F/C	0.9858	likely_pathogenic	0.9896	pathogenic	-1.92	Destabilizing	0.999	D	0.835	deleterious	D	0.549299436	None	None	N
F/D	0.999	likely_pathogenic	0.9991	pathogenic	-2.722	Highly Destabilizing	0.998	D	0.84	deleterious	None	None	None	None	N
F/E	0.9992	likely_pathogenic	0.9991	pathogenic	-2.605	Highly Destabilizing	0.998	D	0.84	deleterious	None	None	None	None	N
F/G	0.9985	likely_pathogenic	0.9989	pathogenic	-3.246	Highly Destabilizing	0.998	D	0.829	deleterious	None	None	None	None	N
F/H	0.9956	likely_pathogenic	0.9954	pathogenic	-1.545	Destabilizing	0.999	D	0.721	prob.delet.	None	None	None	None	N
F/I	0.9268	likely_pathogenic	0.9256	pathogenic	-1.709	Destabilizing	0.1	N	0.477	neutral	N	0.489330542	None	None	N
F/K	0.9991	likely_pathogenic	0.9989	pathogenic	-1.707	Destabilizing	0.993	D	0.839	deleterious	None	None	None	None	N
F/L	0.9965	likely_pathogenic	0.9972	pathogenic	-1.709	Destabilizing	0.76	D	0.627	neutral	N	0.516036533	None	None	N
F/M	0.9765	likely_pathogenic	0.9759	pathogenic	-1.556	Destabilizing	0.986	D	0.681	prob.neutral	None	None	None	None	N
F/N	0.9964	likely_pathogenic	0.9962	pathogenic	-1.868	Destabilizing	0.998	D	0.847	deleterious	None	None	None	None	N
F/P	0.9996	likely_pathogenic	0.9997	pathogenic	-2.102	Highly Destabilizing	0.998	D	0.853	deleterious	None	None	None	None	N
F/Q	0.999	likely_pathogenic	0.9989	pathogenic	-2.024	Highly Destabilizing	0.999	D	0.852	deleterious	None	None	None	None	N
F/R	0.9981	likely_pathogenic	0.998	pathogenic	-0.968	Destabilizing	0.998	D	0.857	deleterious	None	None	None	None	N
F/S	0.9979	likely_pathogenic	0.9983	pathogenic	-2.603	Highly Destabilizing	0.991	D	0.822	deleterious	D	0.566896712	None	None	N
F/T	0.9979	likely_pathogenic	0.9979	pathogenic	-2.386	Highly Destabilizing	0.986	D	0.799	deleterious	None	None	None	None	N
F/V	0.9509	likely_pathogenic	0.9522	pathogenic	-2.102	Highly Destabilizing	0.885	D	0.668	neutral	N	0.517251074	None	None	N
F/W	0.9516	likely_pathogenic	0.964	pathogenic	-0.635	Destabilizing	0.999	D	0.681	prob.neutral	None	None	None	None	N
F/Y	0.74	likely_pathogenic	0.7653	pathogenic	-0.921	Destabilizing	0.99	D	0.643	neutral	D	0.567150202	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.