TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25786	77581;77582;77583	chr2:178568776;178568775;178568774	chr2:179433503;179433502;179433501
N2AB	24145	72658;72659;72660	chr2:178568776;178568775;178568774	chr2:179433503;179433502;179433501
N2A	23218	69877;69878;69879	chr2:178568776;178568775;178568774	chr2:179433503;179433502;179433501
N2B	16721	50386;50387;50388	chr2:178568776;178568775;178568774	chr2:179433503;179433502;179433501
Novex-1	16846	50761;50762;50763	chr2:178568776;178568775;178568774	chr2:179433503;179433502;179433501
Novex-2	16913	50962;50963;50964	chr2:178568776;178568775;178568774	chr2:179433503;179433502;179433501
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Fn3-75
• Domain position: 89
• Structural Position: 124
• Q(SASA): 0.5402
• 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
A/E	None	None	0.987	N	0.654	0.243	0.457286136841	gnomAD-4.0.0	2.73837E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.59923E-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
A/C	0.7065	likely_pathogenic	0.6882	pathogenic	-1.028	Destabilizing	0.999	D	0.559	neutral	None	None	None	None	I
A/D	0.6382	likely_pathogenic	0.6102	pathogenic	-0.546	Destabilizing	0.98	D	0.659	prob.neutral	None	None	None	None	I
A/E	0.6399	likely_pathogenic	0.6246	pathogenic	-0.659	Destabilizing	0.987	D	0.654	prob.neutral	N	0.484768873	None	None	I
A/F	0.6006	likely_pathogenic	0.5709	pathogenic	-0.9	Destabilizing	0.997	D	0.667	prob.neutral	None	None	None	None	I
A/G	0.1684	likely_benign	0.1627	benign	-0.427	Destabilizing	0.014	N	0.174	neutral	N	0.439055226	None	None	I
A/H	0.7441	likely_pathogenic	0.7218	pathogenic	-0.225	Destabilizing	0.999	D	0.665	prob.neutral	None	None	None	None	I
A/I	0.4598	ambiguous	0.4294	ambiguous	-0.475	Destabilizing	0.997	D	0.623	neutral	None	None	None	None	I
A/K	0.8436	likely_pathogenic	0.8254	pathogenic	-0.708	Destabilizing	0.98	D	0.657	prob.neutral	None	None	None	None	I
A/L	0.2915	likely_benign	0.2705	benign	-0.475	Destabilizing	0.99	D	0.6	neutral	None	None	None	None	I
A/M	0.3923	ambiguous	0.3701	ambiguous	-0.823	Destabilizing	0.999	D	0.625	neutral	None	None	None	None	I
A/N	0.4513	ambiguous	0.433	ambiguous	-0.539	Destabilizing	0.98	D	0.659	prob.neutral	None	None	None	None	I
A/P	0.2271	likely_benign	0.2296	benign	-0.424	Destabilizing	0.996	D	0.633	neutral	N	0.474071877	None	None	I
A/Q	0.6109	likely_pathogenic	0.5959	pathogenic	-0.723	Destabilizing	0.997	D	0.646	neutral	None	None	None	None	I
A/R	0.7703	likely_pathogenic	0.75	pathogenic	-0.302	Destabilizing	0.99	D	0.622	neutral	None	None	None	None	I
A/S	0.1286	likely_benign	0.1223	benign	-0.75	Destabilizing	0.914	D	0.383	neutral	N	0.373310237	None	None	I
A/T	0.1614	likely_benign	0.1566	benign	-0.782	Destabilizing	0.987	D	0.6	neutral	N	0.445133049	None	None	I
A/V	0.2214	likely_benign	0.2098	benign	-0.424	Destabilizing	0.987	D	0.581	neutral	N	0.46415874	None	None	I
A/W	0.903	likely_pathogenic	0.8814	pathogenic	-1.001	Destabilizing	0.999	D	0.668	prob.neutral	None	None	None	None	I
A/Y	0.7504	likely_pathogenic	0.7273	pathogenic	-0.714	Destabilizing	0.999	D	0.664	prob.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.