TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18538	55837;55838;55839	chr2:178601385;178601384;178601383	chr2:179466112;179466111;179466110
N2AB	16897	50914;50915;50916	chr2:178601385;178601384;178601383	chr2:179466112;179466111;179466110
N2A	15970	48133;48134;48135	chr2:178601385;178601384;178601383	chr2:179466112;179466111;179466110
N2B	9473	28642;28643;28644	chr2:178601385;178601384;178601383	chr2:179466112;179466111;179466110
Novex-1	9598	29017;29018;29019	chr2:178601385;178601384;178601383	chr2:179466112;179466111;179466110
Novex-2	9665	29218;29219;29220	chr2:178601385;178601384;178601383	chr2:179466112;179466111;179466110
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: Fn3-22
• Domain position: 60
• Structural Position: 91
• Q(SASA): 0.1401
• 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/S	None	None	0.801	N	0.549	0.349	0.68170140072	gnomAD-4.0.0	1.59342E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.4346E-05	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	0.7521	likely_pathogenic	0.8813	pathogenic	-2.578	Highly Destabilizing	0.842	D	0.541	neutral	None	None	None	None	N
F/C	0.4322	ambiguous	0.5886	pathogenic	-1.651	Destabilizing	0.997	D	0.617	neutral	N	0.435249704	None	None	N
F/D	0.9821	likely_pathogenic	0.9903	pathogenic	-2.729	Highly Destabilizing	0.016	N	0.53	neutral	None	None	None	None	N
F/E	0.9799	likely_pathogenic	0.9891	pathogenic	-2.527	Highly Destabilizing	0.728	D	0.56	neutral	None	None	None	None	N
F/G	0.9261	likely_pathogenic	0.9663	pathogenic	-3.02	Highly Destabilizing	0.915	D	0.562	neutral	None	None	None	None	N
F/H	0.7773	likely_pathogenic	0.8188	pathogenic	-1.485	Destabilizing	0.949	D	0.557	neutral	None	None	None	None	N
F/I	0.5167	ambiguous	0.7017	pathogenic	-1.158	Destabilizing	0.669	D	0.439	neutral	N	0.479539198	None	None	N
F/K	0.9746	likely_pathogenic	0.9867	pathogenic	-2.075	Highly Destabilizing	0.974	D	0.631	neutral	None	None	None	None	N
F/L	0.8729	likely_pathogenic	0.9393	pathogenic	-1.158	Destabilizing	0.005	N	0.186	neutral	N	0.430475815	None	None	N
F/M	0.6151	likely_pathogenic	0.7399	pathogenic	-0.845	Destabilizing	0.949	D	0.485	neutral	None	None	None	None	N
F/N	0.9387	likely_pathogenic	0.9609	pathogenic	-2.53	Highly Destabilizing	0.949	D	0.637	neutral	None	None	None	None	N
F/P	0.9987	likely_pathogenic	0.9996	pathogenic	-1.64	Destabilizing	0.991	D	0.638	neutral	None	None	None	None	N
F/Q	0.9455	likely_pathogenic	0.967	pathogenic	-2.452	Highly Destabilizing	0.974	D	0.635	neutral	None	None	None	None	N
F/R	0.9404	likely_pathogenic	0.9673	pathogenic	-1.61	Destabilizing	0.974	D	0.637	neutral	None	None	None	None	N
F/S	0.7785	likely_pathogenic	0.8897	pathogenic	-3.193	Highly Destabilizing	0.801	D	0.549	neutral	N	0.504995003	None	None	N
F/T	0.8332	likely_pathogenic	0.9192	pathogenic	-2.878	Highly Destabilizing	0.915	D	0.557	neutral	None	None	None	None	N
F/V	0.4327	ambiguous	0.6299	pathogenic	-1.64	Destabilizing	0.669	D	0.506	neutral	N	0.440708665	None	None	N
F/W	0.5379	ambiguous	0.5712	pathogenic	-0.236	Destabilizing	0.974	D	0.499	neutral	None	None	None	None	N
F/Y	0.1781	likely_benign	0.1918	benign	-0.593	Destabilizing	0.005	N	0.168	neutral	N	0.39651517	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.