TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9746	29461;29462;29463	chr2:178706638;178706637;178706636	chr2:179571365;179571364;179571363
N2AB	9429	28510;28511;28512	chr2:178706638;178706637;178706636	chr2:179571365;179571364;179571363
N2A	8502	25729;25730;25731	chr2:178706638;178706637;178706636	chr2:179571365;179571364;179571363
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-83
• Domain position: 49
• Structural Position: 122
• Q(SASA): 0.2719
• 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	None	None	0.131	0.093	0.372268306217	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-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	0.2898	likely_benign	0.2678	benign	-2.24	Highly Destabilizing	0.002	N	0.272	neutral	None	None	None	None	N
F/C	0.2351	likely_benign	0.1929	benign	-0.963	Destabilizing	0.427	N	0.416	neutral	None	None	None	None	N
F/D	0.6699	likely_pathogenic	0.5701	pathogenic	-0.642	Destabilizing	0.018	N	0.416	neutral	None	None	None	None	N
F/E	0.683	likely_pathogenic	0.6261	pathogenic	-0.586	Destabilizing	0.009	N	0.369	neutral	None	None	None	None	N
F/G	0.6649	likely_pathogenic	0.5535	ambiguous	-2.551	Highly Destabilizing	0.009	N	0.351	neutral	None	None	None	None	N
F/H	0.2998	likely_benign	0.306	benign	-0.765	Destabilizing	None	N	0.216	neutral	None	None	None	None	N
F/I	0.0993	likely_benign	0.0898	benign	-1.321	Destabilizing	None	N	0.079	neutral	None	None	None	None	N
F/K	0.6031	likely_pathogenic	0.5659	pathogenic	-1.002	Destabilizing	0.018	N	0.378	neutral	None	None	None	None	N
F/L	0.4035	ambiguous	0.4117	ambiguous	-1.321	Destabilizing	None	N	0.075	neutral	None	None	None	None	N
F/M	0.2597	likely_benign	0.2628	benign	-0.938	Destabilizing	0.022	N	0.333	neutral	None	None	None	None	N
F/N	0.3601	ambiguous	0.3089	benign	-0.901	Destabilizing	0.009	N	0.415	neutral	None	None	None	None	N
F/P	0.9917	likely_pathogenic	0.9725	pathogenic	-1.619	Destabilizing	0.085	N	0.5	neutral	None	None	None	None	N
F/Q	0.4874	ambiguous	0.4624	ambiguous	-1.055	Destabilizing	0.044	N	0.499	neutral	None	None	None	None	N
F/R	0.4836	ambiguous	0.4296	ambiguous	-0.273	Destabilizing	0.044	N	0.481	neutral	None	None	None	None	N
F/S	0.1941	likely_benign	0.1611	benign	-1.748	Destabilizing	None	N	0.131	neutral	None	None	None	None	N
F/T	0.2403	likely_benign	0.2162	benign	-1.606	Destabilizing	None	N	0.149	neutral	None	None	None	None	N
F/V	0.1037	likely_benign	0.0986	benign	-1.619	Destabilizing	None	N	0.115	neutral	None	None	None	None	N
F/W	0.3946	ambiguous	0.3573	ambiguous	-0.506	Destabilizing	0.497	N	0.362	neutral	None	None	None	None	N
F/Y	0.1551	likely_benign	0.1447	benign	-0.686	Destabilizing	0.007	N	0.317	neutral	None	None	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.