TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22290	67093;67094;67095	chr2:178580511;178580510;178580509	chr2:179445238;179445237;179445236
N2AB	20649	62170;62171;62172	chr2:178580511;178580510;178580509	chr2:179445238;179445237;179445236
N2A	19722	59389;59390;59391	chr2:178580511;178580510;178580509	chr2:179445238;179445237;179445236
N2B	13225	39898;39899;39900	chr2:178580511;178580510;178580509	chr2:179445238;179445237;179445236
Novex-1	13350	40273;40274;40275	chr2:178580511;178580510;178580509	chr2:179445238;179445237;179445236
Novex-2	13417	40474;40475;40476	chr2:178580511;178580510;178580509	chr2:179445238;179445237;179445236
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Ig-126
• Domain position: 26
• Structural Position: 43
• Q(SASA): 0.465
• 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
P/S	None	None	0.811	N	0.446	0.152	0.298056030225	gnomAD-4.0.0	1.59328E-06	None	None	None	None	I	None	0	0	None	4.77236E-05	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
P/A	0.0581	likely_benign	0.0573	benign	-0.865	Destabilizing	0.004	N	0.331	neutral	N	0.43553021	None	None	I
P/C	0.509	ambiguous	0.5001	ambiguous	-0.593	Destabilizing	0.999	D	0.662	neutral	None	None	None	None	I
P/D	0.667	likely_pathogenic	0.6671	pathogenic	-0.481	Destabilizing	0.988	D	0.423	neutral	None	None	None	None	I
P/E	0.3682	ambiguous	0.3661	ambiguous	-0.563	Destabilizing	0.919	D	0.419	neutral	None	None	None	None	I
P/F	0.5239	ambiguous	0.5005	ambiguous	-0.885	Destabilizing	0.996	D	0.657	neutral	None	None	None	None	I
P/G	0.4309	ambiguous	0.4172	ambiguous	-1.069	Destabilizing	0.851	D	0.539	neutral	None	None	None	None	I
P/H	0.2764	likely_benign	0.2661	benign	-0.638	Destabilizing	0.999	D	0.634	neutral	D	0.534520982	None	None	I
P/I	0.2064	likely_benign	0.1996	benign	-0.454	Destabilizing	0.976	D	0.649	neutral	None	None	None	None	I
P/K	0.3149	likely_benign	0.3145	benign	-0.693	Destabilizing	0.919	D	0.425	neutral	None	None	None	None	I
P/L	0.1203	likely_benign	0.1143	benign	-0.454	Destabilizing	0.896	D	0.603	neutral	N	0.474741959	None	None	I
P/M	0.2459	likely_benign	0.2474	benign	-0.379	Destabilizing	0.999	D	0.631	neutral	None	None	None	None	I
P/N	0.4243	ambiguous	0.4303	ambiguous	-0.345	Destabilizing	0.988	D	0.618	neutral	None	None	None	None	I
P/Q	0.1771	likely_benign	0.1784	benign	-0.578	Destabilizing	0.988	D	0.439	neutral	None	None	None	None	I
P/R	0.2505	likely_benign	0.2383	benign	-0.166	Destabilizing	0.984	D	0.623	neutral	N	0.451846457	None	None	I
P/S	0.1305	likely_benign	0.1286	benign	-0.77	Destabilizing	0.811	D	0.446	neutral	N	0.480955856	None	None	I
P/T	0.0966	likely_benign	0.0968	benign	-0.749	Destabilizing	0.896	D	0.447	neutral	N	0.420464757	None	None	I
P/V	0.1401	likely_benign	0.1385	benign	-0.555	Destabilizing	0.851	D	0.555	neutral	None	None	None	None	I
P/W	0.8214	likely_pathogenic	0.8013	pathogenic	-0.982	Destabilizing	0.999	D	0.694	prob.neutral	None	None	None	None	I
P/Y	0.5116	ambiguous	0.4936	ambiguous	-0.698	Destabilizing	0.996	D	0.658	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.