TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19815	59668;59669;59670	chr2:178592562;178592561;178592560	chr2:179457289;179457288;179457287
N2AB	18174	54745;54746;54747	chr2:178592562;178592561;178592560	chr2:179457289;179457288;179457287
N2A	17247	51964;51965;51966	chr2:178592562;178592561;178592560	chr2:179457289;179457288;179457287
N2B	10750	32473;32474;32475	chr2:178592562;178592561;178592560	chr2:179457289;179457288;179457287
Novex-1	10875	32848;32849;32850	chr2:178592562;178592561;178592560	chr2:179457289;179457288;179457287
Novex-2	10942	33049;33050;33051	chr2:178592562;178592561;178592560	chr2:179457289;179457288;179457287
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-119
• Domain position: 26
• Structural Position: 43
• Q(SASA): 0.4583
• 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	0.999	N	0.614	0.395	0.568180043242	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	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	0.58	likely_pathogenic	0.58	pathogenic	-2.07	Highly Destabilizing	1.0	D	0.659	neutral	None	None	None	None	I
F/C	0.498	ambiguous	0.4134	ambiguous	-0.913	Destabilizing	1.0	D	0.668	neutral	N	0.4949984	None	None	I
F/D	0.842	likely_pathogenic	0.8686	pathogenic	-0.728	Destabilizing	1.0	D	0.669	neutral	None	None	None	None	I
F/E	0.8375	likely_pathogenic	0.866	pathogenic	-0.65	Destabilizing	1.0	D	0.664	neutral	None	None	None	None	I
F/G	0.8858	likely_pathogenic	0.8898	pathogenic	-2.402	Highly Destabilizing	1.0	D	0.675	neutral	None	None	None	None	I
F/H	0.6565	likely_pathogenic	0.6558	pathogenic	-0.777	Destabilizing	1.0	D	0.631	neutral	None	None	None	None	I
F/I	0.3264	likely_benign	0.2845	benign	-1.081	Destabilizing	1.0	D	0.698	prob.neutral	N	0.447555358	None	None	I
F/K	0.837	likely_pathogenic	0.8675	pathogenic	-1.081	Destabilizing	1.0	D	0.667	neutral	None	None	None	None	I
F/L	0.8685	likely_pathogenic	0.8446	pathogenic	-1.081	Destabilizing	0.999	D	0.614	neutral	N	0.460599226	None	None	I
F/M	0.5733	likely_pathogenic	0.5503	ambiguous	-0.73	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	I
F/N	0.6749	likely_pathogenic	0.6817	pathogenic	-1.089	Destabilizing	1.0	D	0.673	neutral	None	None	None	None	I
F/P	0.8537	likely_pathogenic	0.851	pathogenic	-1.403	Destabilizing	1.0	D	0.659	neutral	None	None	None	None	I
F/Q	0.7574	likely_pathogenic	0.7803	pathogenic	-1.157	Destabilizing	1.0	D	0.661	neutral	None	None	None	None	I
F/R	0.7666	likely_pathogenic	0.7928	pathogenic	-0.471	Destabilizing	1.0	D	0.674	neutral	None	None	None	None	I
F/S	0.4779	ambiguous	0.4742	ambiguous	-1.872	Destabilizing	1.0	D	0.688	prob.neutral	N	0.472469658	None	None	I
F/T	0.5808	likely_pathogenic	0.5715	pathogenic	-1.701	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	I
F/V	0.2903	likely_benign	0.2595	benign	-1.403	Destabilizing	1.0	D	0.658	neutral	N	0.465447685	None	None	I
F/W	0.6602	likely_pathogenic	0.6613	pathogenic	-0.38	Destabilizing	1.0	D	0.665	neutral	None	None	None	None	I
F/Y	0.2029	likely_benign	0.1931	benign	-0.555	Destabilizing	0.999	D	0.605	neutral	N	0.504832793	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.