TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32341	97246;97247;97248	chr2:178542833;178542832;178542831	chr2:179407560;179407559;179407558
N2AB	30700	92323;92324;92325	chr2:178542833;178542832;178542831	chr2:179407560;179407559;179407558
N2A	29773	89542;89543;89544	chr2:178542833;178542832;178542831	chr2:179407560;179407559;179407558
N2B	23276	70051;70052;70053	chr2:178542833;178542832;178542831	chr2:179407560;179407559;179407558
Novex-1	23401	70426;70427;70428	chr2:178542833;178542832;178542831	chr2:179407560;179407559;179407558
Novex-2	23468	70627;70628;70629	chr2:178542833;178542832;178542831	chr2:179407560;179407559;179407558
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-154
• Domain position: 35
• Structural Position: 49
• Q(SASA): 0.161
• 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	0.961	N	0.495	0.283	0.422404719673	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	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	0.6025	likely_pathogenic	0.5043	ambiguous	-2.301	Highly Destabilizing	0.942	D	0.575	neutral	None	None	None	None	N
F/C	0.2965	likely_benign	0.2395	benign	-1.362	Destabilizing	1.0	D	0.695	prob.neutral	N	0.516163641	None	None	N
F/D	0.8511	likely_pathogenic	0.7904	pathogenic	-0.909	Destabilizing	0.991	D	0.706	prob.neutral	None	None	None	None	N
F/E	0.8345	likely_pathogenic	0.776	pathogenic	-0.818	Destabilizing	0.991	D	0.695	prob.neutral	None	None	None	None	N
F/G	0.7689	likely_pathogenic	0.6883	pathogenic	-2.634	Highly Destabilizing	0.97	D	0.647	neutral	None	None	None	None	N
F/H	0.3645	ambiguous	0.3109	benign	-0.915	Destabilizing	0.991	D	0.649	neutral	None	None	None	None	N
F/I	0.2914	likely_benign	0.2356	benign	-1.294	Destabilizing	0.98	D	0.525	neutral	N	0.450304009	None	None	N
F/K	0.7541	likely_pathogenic	0.678	pathogenic	-1.077	Destabilizing	0.991	D	0.695	prob.neutral	None	None	None	None	N
F/L	0.8135	likely_pathogenic	0.7589	pathogenic	-1.294	Destabilizing	0.961	D	0.495	neutral	N	0.393543862	None	None	N
F/M	0.5174	ambiguous	0.4734	ambiguous	-1.09	Destabilizing	0.999	D	0.56	neutral	None	None	None	None	N
F/N	0.4773	ambiguous	0.4223	ambiguous	-1.046	Destabilizing	0.991	D	0.715	prob.delet.	None	None	None	None	N
F/P	0.998	likely_pathogenic	0.9962	pathogenic	-1.624	Destabilizing	0.996	D	0.74	deleterious	None	None	None	None	N
F/Q	0.6718	likely_pathogenic	0.5783	pathogenic	-1.177	Destabilizing	0.996	D	0.742	deleterious	None	None	None	None	N
F/R	0.6405	likely_pathogenic	0.5327	ambiguous	-0.424	Destabilizing	0.996	D	0.734	prob.delet.	None	None	None	None	N
F/S	0.3421	ambiguous	0.2742	benign	-1.952	Destabilizing	0.489	N	0.371	neutral	N	0.422733405	None	None	N
F/T	0.4685	ambiguous	0.4071	ambiguous	-1.769	Destabilizing	0.942	D	0.621	neutral	None	None	None	None	N
F/V	0.281	likely_benign	0.2291	benign	-1.624	Destabilizing	0.961	D	0.554	neutral	N	0.466734899	None	None	N
F/W	0.4341	ambiguous	0.3893	ambiguous	-0.413	Destabilizing	1.0	D	0.546	neutral	None	None	None	None	N
F/Y	0.0795	likely_benign	0.0786	benign	-0.589	Destabilizing	0.248	N	0.347	neutral	N	0.394005222	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.