TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18546	55861;55862;55863	chr2:178601361;178601360;178601359	chr2:179466088;179466087;179466086
N2AB	16905	50938;50939;50940	chr2:178601361;178601360;178601359	chr2:179466088;179466087;179466086
N2A	15978	48157;48158;48159	chr2:178601361;178601360;178601359	chr2:179466088;179466087;179466086
N2B	9481	28666;28667;28668	chr2:178601361;178601360;178601359	chr2:179466088;179466087;179466086
Novex-1	9606	29041;29042;29043	chr2:178601361;178601360;178601359	chr2:179466088;179466087;179466086
Novex-2	9673	29242;29243;29244	chr2:178601361;178601360;178601359	chr2:179466088;179466087;179466086
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: Fn3-22
• Domain position: 68
• Structural Position: 100
• Q(SASA): 0.5853
• 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/Q	None	None	0.001	N	0.213	0.101	0.17948927462	gnomAD-4.0.0	1.59393E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43554E-05	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	0.2107	likely_benign	0.1665	benign	-0.404	Destabilizing	0.005	N	0.397	neutral	N	0.408908464	None	None	N
E/C	0.7916	likely_pathogenic	0.7414	pathogenic	0.084	Stabilizing	0.864	D	0.577	neutral	None	None	None	None	N
E/D	0.0844	likely_benign	0.0793	benign	-0.381	Destabilizing	0.024	N	0.412	neutral	N	0.398787471	None	None	N
E/F	0.8052	likely_pathogenic	0.7484	pathogenic	-0.439	Destabilizing	0.628	D	0.601	neutral	None	None	None	None	N
E/G	0.0865	likely_benign	0.063	benign	-0.614	Destabilizing	None	N	0.323	neutral	N	0.272143165	None	None	N
E/H	0.4284	ambiguous	0.3738	ambiguous	-0.437	Destabilizing	0.356	N	0.432	neutral	None	None	None	None	N
E/I	0.6316	likely_pathogenic	0.546	ambiguous	0.114	Stabilizing	0.356	N	0.603	neutral	None	None	None	None	N
E/K	0.2072	likely_benign	0.1623	benign	0.203	Stabilizing	0.012	N	0.406	neutral	N	0.422107048	None	None	N
E/L	0.5001	ambiguous	0.4178	ambiguous	0.114	Stabilizing	0.072	N	0.613	neutral	None	None	None	None	N
E/M	0.5736	likely_pathogenic	0.4934	ambiguous	0.366	Stabilizing	0.356	N	0.572	neutral	None	None	None	None	N
E/N	0.1623	likely_benign	0.1506	benign	0.039	Stabilizing	0.072	N	0.353	neutral	None	None	None	None	N
E/P	0.6866	likely_pathogenic	0.6003	pathogenic	-0.038	Destabilizing	0.136	N	0.525	neutral	None	None	None	None	N
E/Q	0.1506	likely_benign	0.126	benign	0.053	Stabilizing	0.001	N	0.213	neutral	N	0.43043853	None	None	N
E/R	0.3129	likely_benign	0.2453	benign	0.315	Stabilizing	0.038	N	0.347	neutral	None	None	None	None	N
E/S	0.1509	likely_benign	0.1296	benign	-0.171	Destabilizing	0.016	N	0.395	neutral	None	None	None	None	N
E/T	0.2625	likely_benign	0.2217	benign	-0.011	Destabilizing	0.072	N	0.514	neutral	None	None	None	None	N
E/V	0.4433	ambiguous	0.3643	ambiguous	-0.038	Destabilizing	0.055	N	0.585	neutral	N	0.460318719	None	None	N
E/W	0.9111	likely_pathogenic	0.859	pathogenic	-0.345	Destabilizing	0.864	D	0.577	neutral	None	None	None	None	N
E/Y	0.638	likely_pathogenic	0.5752	pathogenic	-0.212	Destabilizing	0.356	N	0.586	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.