TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7939	24040;24041;24042	chr2:178719677;178719676;178719675	chr2:179584404;179584403;179584402
N2AB	7622	23089;23090;23091	chr2:178719677;178719676;178719675	chr2:179584404;179584403;179584402
N2A	6695	20308;20309;20310	chr2:178719677;178719676;178719675	chr2:179584404;179584403;179584402
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-64
• Domain position: 51
• Structural Position: 127
• Q(SASA): 0.3535
• 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	rs866647945	None	0.015	N	0.301	0.183	0.104622674875	gnomAD-4.0.0	6.84224E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.65673E-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	0.8532	likely_pathogenic	0.8613	pathogenic	-1.926	Destabilizing	0.939	D	0.618	neutral	None	None	None	None	N
F/C	0.6535	likely_pathogenic	0.656	pathogenic	-1.107	Destabilizing	0.999	D	0.669	neutral	N	0.51624298	None	None	N
F/D	0.9561	likely_pathogenic	0.9557	pathogenic	-0.359	Destabilizing	0.997	D	0.687	prob.neutral	None	None	None	None	N
F/E	0.957	likely_pathogenic	0.9572	pathogenic	-0.248	Destabilizing	0.997	D	0.688	prob.neutral	None	None	None	None	N
F/G	0.9421	likely_pathogenic	0.9453	pathogenic	-2.279	Highly Destabilizing	0.991	D	0.678	prob.neutral	None	None	None	None	N
F/H	0.8368	likely_pathogenic	0.8337	pathogenic	-0.572	Destabilizing	0.999	D	0.595	neutral	None	None	None	None	N
F/I	0.33	likely_benign	0.3376	benign	-0.871	Destabilizing	0.704	D	0.509	neutral	N	0.482490006	None	None	N
F/K	0.9648	likely_pathogenic	0.9615	pathogenic	-1.092	Destabilizing	0.991	D	0.682	prob.neutral	None	None	None	None	N
F/L	0.8628	likely_pathogenic	0.8549	pathogenic	-0.871	Destabilizing	0.015	N	0.301	neutral	N	0.487593826	None	None	N
F/M	0.6102	likely_pathogenic	0.6178	pathogenic	-0.7	Destabilizing	0.579	D	0.321	neutral	None	None	None	None	N
F/N	0.8839	likely_pathogenic	0.8766	pathogenic	-1.209	Destabilizing	0.997	D	0.681	prob.neutral	None	None	None	None	N
F/P	0.9963	likely_pathogenic	0.9961	pathogenic	-1.216	Destabilizing	0.997	D	0.683	prob.neutral	None	None	None	None	N
F/Q	0.9288	likely_pathogenic	0.9252	pathogenic	-1.183	Destabilizing	0.991	D	0.683	prob.neutral	None	None	None	None	N
F/R	0.9156	likely_pathogenic	0.9121	pathogenic	-0.582	Destabilizing	0.991	D	0.683	prob.neutral	None	None	None	None	N
F/S	0.7488	likely_pathogenic	0.7639	pathogenic	-2.061	Highly Destabilizing	0.988	D	0.678	prob.neutral	N	0.500811053	None	None	N
F/T	0.7872	likely_pathogenic	0.7961	pathogenic	-1.851	Destabilizing	0.939	D	0.674	neutral	None	None	None	None	N
F/V	0.3219	likely_benign	0.3315	benign	-1.216	Destabilizing	0.134	N	0.406	neutral	N	0.493845008	None	None	N
F/W	0.6417	likely_pathogenic	0.6468	pathogenic	0.014	Stabilizing	0.999	D	0.603	neutral	None	None	None	None	N
F/Y	0.2806	likely_benign	0.2749	benign	-0.237	Destabilizing	0.986	D	0.581	neutral	N	0.503235282	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.