TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6884	20875;20876;20877	chr2:178725554;178725553;178725552	chr2:179590281;179590280;179590279
N2AB	6567	19924;19925;19926	chr2:178725554;178725553;178725552	chr2:179590281;179590280;179590279
N2A	5640	17143;17144;17145	chr2:178725554;178725553;178725552	chr2:179590281;179590280;179590279
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: TTT
• RefSeq wild type template codon: AAA
• Domain: Ig-53
• Domain position: 31
• Structural Position: 45
• Q(SASA): 0.6705
• 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	None	None	0.001	N	0.208	0.056	0.270447802918	gnomAD-4.0.0	1.59276E-06	None	None	None	None	N	None	5.66701E-05	0	None	0	0	None	0	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	0.1007	likely_benign	0.0849	benign	-1.398	Destabilizing	None	N	0.197	neutral	None	None	None	None	N
F/C	0.1669	likely_benign	0.1299	benign	-0.595	Destabilizing	0.103	N	0.479	neutral	N	0.43048975	None	None	N
F/D	0.2827	likely_benign	0.2459	benign	-0.058	Destabilizing	None	N	0.296	neutral	None	None	None	None	N
F/E	0.3839	ambiguous	0.3478	ambiguous	-0.051	Destabilizing	0.001	N	0.319	neutral	None	None	None	None	N
F/G	0.3203	likely_benign	0.2686	benign	-1.633	Destabilizing	0.001	N	0.344	neutral	None	None	None	None	N
F/H	0.2181	likely_benign	0.1916	benign	-0.046	Destabilizing	0.132	N	0.493	neutral	None	None	None	None	N
F/I	0.0907	likely_benign	0.0759	benign	-0.749	Destabilizing	0.001	N	0.201	neutral	N	0.392528794	None	None	N
F/K	0.4614	ambiguous	0.4005	ambiguous	-0.626	Destabilizing	0.002	N	0.316	neutral	None	None	None	None	N
F/L	0.3663	ambiguous	0.3157	benign	-0.749	Destabilizing	0.001	N	0.208	neutral	N	0.386429541	None	None	N
F/M	0.225	likely_benign	0.1881	benign	-0.621	Destabilizing	0.041	N	0.417	neutral	None	None	None	None	N
F/N	0.1609	likely_benign	0.1362	benign	-0.653	Destabilizing	0.002	N	0.326	neutral	None	None	None	None	N
F/P	0.845	likely_pathogenic	0.8129	pathogenic	-0.951	Destabilizing	0.009	N	0.345	neutral	None	None	None	None	N
F/Q	0.352	ambiguous	0.2979	benign	-0.727	Destabilizing	0.009	N	0.438	neutral	None	None	None	None	N
F/R	0.3384	likely_benign	0.2984	benign	-0.04	Destabilizing	0.009	N	0.413	neutral	None	None	None	None	N
F/S	0.0635	likely_benign	0.0578	benign	-1.288	Destabilizing	None	N	0.206	neutral	N	0.270351732	None	None	N
F/T	0.077	likely_benign	0.0639	benign	-1.189	Destabilizing	None	N	0.198	neutral	None	None	None	None	N
F/V	0.0865	likely_benign	0.0722	benign	-0.951	Destabilizing	None	N	0.177	neutral	N	0.381234365	None	None	N
F/W	0.3084	likely_benign	0.2896	benign	-0.355	Destabilizing	0.316	N	0.403	neutral	None	None	None	None	N
F/Y	0.0941	likely_benign	0.0901	benign	-0.447	Destabilizing	0.013	N	0.392	neutral	N	0.430316392	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.