TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18561	55906;55907;55908	chr2:178601316;178601315;178601314	chr2:179466043;179466042;179466041
N2AB	16920	50983;50984;50985	chr2:178601316;178601315;178601314	chr2:179466043;179466042;179466041
N2A	15993	48202;48203;48204	chr2:178601316;178601315;178601314	chr2:179466043;179466042;179466041
N2B	9496	28711;28712;28713	chr2:178601316;178601315;178601314	chr2:179466043;179466042;179466041
Novex-1	9621	29086;29087;29088	chr2:178601316;178601315;178601314	chr2:179466043;179466042;179466041
Novex-2	9688	29287;29288;29289	chr2:178601316;178601315;178601314	chr2:179466043;179466042;179466041
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-22
• Domain position: 83
• Structural Position: 117
• Q(SASA): 0.4197
• 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
I/V	rs1327467989	-1.127	None	N	0.204	0.036	0.132336055621	gnomAD-2.1.1	4.09E-06	None	None	None	None	I	None	6.48E-05	0	None	0	0	None	0	None	0	0	0
I/V	rs1327467989	-1.127	None	N	0.204	0.036	0.132336055621	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
I/V	rs1327467989	-1.127	None	N	0.204	0.036	0.132336055621	gnomAD-4.0.0	6.57696E-06	None	None	None	None	I	None	2.41289E-05	0	None	0	0	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
I/A	0.1311	likely_benign	0.1145	benign	-1.396	Destabilizing	0.035	N	0.528	neutral	None	None	None	None	I
I/C	0.3794	ambiguous	0.3729	ambiguous	-0.909	Destabilizing	0.824	D	0.563	neutral	None	None	None	None	I
I/D	0.546	ambiguous	0.4856	ambiguous	-0.673	Destabilizing	0.38	N	0.599	neutral	None	None	None	None	I
I/E	0.3994	ambiguous	0.3565	ambiguous	-0.712	Destabilizing	0.38	N	0.6	neutral	None	None	None	None	I
I/F	0.1512	likely_benign	0.1126	benign	-1.043	Destabilizing	None	N	0.207	neutral	N	0.442925037	None	None	I
I/G	0.4193	ambiguous	0.3429	ambiguous	-1.664	Destabilizing	0.149	N	0.597	neutral	None	None	None	None	I
I/H	0.3785	ambiguous	0.3399	benign	-0.733	Destabilizing	0.935	D	0.616	neutral	None	None	None	None	I
I/K	0.2923	likely_benign	0.2488	benign	-0.817	Destabilizing	0.38	N	0.599	neutral	None	None	None	None	I
I/L	0.0944	likely_benign	0.0846	benign	-0.765	Destabilizing	0.012	N	0.261	neutral	N	0.440172734	None	None	I
I/M	0.0983	likely_benign	0.0838	benign	-0.614	Destabilizing	0.317	N	0.579	neutral	N	0.469207562	None	None	I
I/N	0.2172	likely_benign	0.1978	benign	-0.601	Destabilizing	0.317	N	0.622	neutral	N	0.505722935	None	None	I
I/P	0.2835	likely_benign	0.2568	benign	-0.942	Destabilizing	0.555	D	0.617	neutral	None	None	None	None	I
I/Q	0.2935	likely_benign	0.272	benign	-0.845	Destabilizing	0.555	D	0.621	neutral	None	None	None	None	I
I/R	0.2393	likely_benign	0.1933	benign	-0.159	Destabilizing	0.555	D	0.618	neutral	None	None	None	None	I
I/S	0.1547	likely_benign	0.142	benign	-1.213	Destabilizing	0.062	N	0.557	neutral	N	0.470957001	None	None	I
I/T	0.0834	likely_benign	0.0765	benign	-1.139	Destabilizing	0.002	N	0.351	neutral	N	0.457489058	None	None	I
I/V	0.0545	likely_benign	0.0535	benign	-0.942	Destabilizing	None	N	0.204	neutral	N	0.418970742	None	None	I
I/W	0.695	likely_pathogenic	0.5834	pathogenic	-1.014	Destabilizing	0.935	D	0.618	neutral	None	None	None	None	I
I/Y	0.4123	ambiguous	0.3595	ambiguous	-0.808	Destabilizing	0.081	N	0.552	neutral	None	None	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.