TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27832	83719;83720;83721	chr2:178562638;178562637;178562636	chr2:179427365;179427364;179427363
N2AB	26191	78796;78797;78798	chr2:178562638;178562637;178562636	chr2:179427365;179427364;179427363
N2A	25264	76015;76016;76017	chr2:178562638;178562637;178562636	chr2:179427365;179427364;179427363
N2B	18767	56524;56525;56526	chr2:178562638;178562637;178562636	chr2:179427365;179427364;179427363
Novex-1	18892	56899;56900;56901	chr2:178562638;178562637;178562636	chr2:179427365;179427364;179427363
Novex-2	18959	57100;57101;57102	chr2:178562638;178562637;178562636	chr2:179427365;179427364;179427363
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-90
• Domain position: 67
• Structural Position: 99
• Q(SASA): 0.604
• 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
E/V	rs746250521	-0.16	0.704	N	0.481	0.371	0.504418060211	gnomAD-2.1.1	4.21E-06	None	None	None	None	N	None	0	0	None	0	5.76E-05	None	0	None	0	0	0
E/V	rs746250521	-0.16	0.704	N	0.481	0.371	0.504418060211	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	1.9305E-04	None	0	0	0	0	0
E/V	rs746250521	-0.16	0.704	N	0.481	0.371	0.504418060211	gnomAD-4.0.0	6.57203E-06	None	None	None	None	N	None	0	0	None	0	1.9305E-04	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
E/A	0.1948	likely_benign	0.2352	benign	-0.366	Destabilizing	0.007	N	0.287	neutral	N	0.500509117	None	None	N
E/C	0.9368	likely_pathogenic	0.9553	pathogenic	0.012	Stabilizing	0.987	D	0.663	neutral	None	None	None	None	N
E/D	0.4081	ambiguous	0.4684	ambiguous	-0.352	Destabilizing	0.221	N	0.532	neutral	N	0.513301741	None	None	N
E/F	0.9516	likely_pathogenic	0.9685	pathogenic	-0.279	Destabilizing	0.975	D	0.641	neutral	None	None	None	None	N
E/G	0.3643	ambiguous	0.455	ambiguous	-0.568	Destabilizing	0.786	D	0.503	neutral	N	0.498413489	None	None	N
E/H	0.8428	likely_pathogenic	0.8864	pathogenic	-0.108	Destabilizing	0.99	D	0.495	neutral	None	None	None	None	N
E/I	0.615	likely_pathogenic	0.6507	pathogenic	0.13	Stabilizing	0.899	D	0.63	neutral	None	None	None	None	N
E/K	0.3981	ambiguous	0.4719	ambiguous	0.333	Stabilizing	0.671	D	0.548	neutral	N	0.494183527	None	None	N
E/L	0.7145	likely_pathogenic	0.7813	pathogenic	0.13	Stabilizing	0.816	D	0.549	neutral	None	None	None	None	N
E/M	0.7141	likely_pathogenic	0.763	pathogenic	0.258	Stabilizing	0.974	D	0.563	neutral	None	None	None	None	N
E/N	0.6299	likely_pathogenic	0.6737	pathogenic	0.054	Stabilizing	0.893	D	0.525	neutral	None	None	None	None	N
E/P	0.494	ambiguous	0.5679	pathogenic	-0.015	Destabilizing	0.728	D	0.492	neutral	None	None	None	None	N
E/Q	0.2638	likely_benign	0.3119	benign	0.079	Stabilizing	0.208	N	0.323	neutral	N	0.466951466	None	None	N
E/R	0.5846	likely_pathogenic	0.6594	pathogenic	0.509	Stabilizing	0.95	D	0.526	neutral	None	None	None	None	N
E/S	0.4104	ambiguous	0.4715	ambiguous	-0.123	Destabilizing	0.594	D	0.513	neutral	None	None	None	None	N
E/T	0.4589	ambiguous	0.5072	ambiguous	0.04	Stabilizing	0.801	D	0.431	neutral	None	None	None	None	N
E/V	0.3749	ambiguous	0.4188	ambiguous	-0.015	Destabilizing	0.704	D	0.481	neutral	N	0.492728724	None	None	N
E/W	0.9855	likely_pathogenic	0.9915	pathogenic	-0.137	Destabilizing	0.999	D	0.675	neutral	None	None	None	None	N
E/Y	0.9088	likely_pathogenic	0.9403	pathogenic	-0.033	Destabilizing	0.997	D	0.583	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.