TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29218	87877;87878;87879	chr2:178557702;178557701;178557700	chr2:179422429;179422428;179422427
N2AB	27577	82954;82955;82956	chr2:178557702;178557701;178557700	chr2:179422429;179422428;179422427
N2A	26650	80173;80174;80175	chr2:178557702;178557701;178557700	chr2:179422429;179422428;179422427
N2B	20153	60682;60683;60684	chr2:178557702;178557701;178557700	chr2:179422429;179422428;179422427
Novex-1	20278	61057;61058;61059	chr2:178557702;178557701;178557700	chr2:179422429;179422428;179422427
Novex-2	20345	61258;61259;61260	chr2:178557702;178557701;178557700	chr2:179422429;179422428;179422427
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: Fn3-100
• Domain position: 82
• Structural Position: 114
• Q(SASA): 0.6208
• Predicted PPI site: I

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	0.896	N	0.446	0.321	0.204665344411	gnomAD-4.0.0	1.59104E-06	None	None	None	None	I	None	0	0	None	0	0	None	1.88232E-05	0	0	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	0.9667	likely_pathogenic	0.9838	pathogenic	-0.928	Destabilizing	0.919	D	0.651	neutral	None	None	None	None	I
F/C	0.8633	likely_pathogenic	0.9311	pathogenic	-0.348	Destabilizing	0.999	D	0.681	prob.neutral	N	0.474901383	None	None	I
F/D	0.989	likely_pathogenic	0.994	pathogenic	0.908	Stabilizing	0.988	D	0.673	neutral	None	None	None	None	I
F/E	0.9926	likely_pathogenic	0.9958	pathogenic	0.886	Stabilizing	0.976	D	0.633	neutral	None	None	None	None	I
F/G	0.9839	likely_pathogenic	0.9899	pathogenic	-1.118	Destabilizing	0.988	D	0.616	neutral	None	None	None	None	I
F/H	0.8759	likely_pathogenic	0.9228	pathogenic	0.258	Stabilizing	0.076	N	0.403	neutral	None	None	None	None	I
F/I	0.9229	likely_pathogenic	0.9361	pathogenic	-0.454	Destabilizing	0.984	D	0.471	neutral	N	0.447560066	None	None	I
F/K	0.9908	likely_pathogenic	0.9937	pathogenic	-0.022	Destabilizing	0.976	D	0.665	neutral	None	None	None	None	I
F/L	0.9897	likely_pathogenic	0.9935	pathogenic	-0.454	Destabilizing	0.896	D	0.446	neutral	N	0.454179394	None	None	I
F/M	0.9437	likely_pathogenic	0.9575	pathogenic	-0.36	Destabilizing	0.999	D	0.468	neutral	None	None	None	None	I
F/N	0.9502	likely_pathogenic	0.9683	pathogenic	0.033	Stabilizing	0.976	D	0.672	neutral	None	None	None	None	I
F/P	0.9993	likely_pathogenic	0.9994	pathogenic	-0.592	Destabilizing	0.996	D	0.677	prob.neutral	None	None	None	None	I
F/Q	0.9783	likely_pathogenic	0.9872	pathogenic	-0.027	Destabilizing	0.976	D	0.669	neutral	None	None	None	None	I
F/R	0.9737	likely_pathogenic	0.9827	pathogenic	0.436	Stabilizing	0.976	D	0.67	neutral	None	None	None	None	I
F/S	0.9378	likely_pathogenic	0.9708	pathogenic	-0.687	Destabilizing	0.968	D	0.613	neutral	N	0.484904946	None	None	I
F/T	0.9756	likely_pathogenic	0.9841	pathogenic	-0.617	Destabilizing	0.988	D	0.619	neutral	None	None	None	None	I
F/V	0.9052	likely_pathogenic	0.9356	pathogenic	-0.592	Destabilizing	0.896	D	0.592	neutral	N	0.447597351	None	None	I
F/W	0.69	likely_pathogenic	0.7332	pathogenic	-0.241	Destabilizing	0.999	D	0.481	neutral	None	None	None	None	I
F/Y	0.1927	likely_benign	0.2339	benign	-0.213	Destabilizing	0.046	N	0.232	neutral	N	0.378124197	None	None	I

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.