TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5630	17113;17114;17115	chr2:178732081;178732080;178732079	chr2:179596808;179596807;179596806
N2AB	5313	16162;16163;16164	chr2:178732081;178732080;178732079	chr2:179596808;179596807;179596806
N2A	4386	13381;13382;13383	chr2:178732081;178732080;178732079	chr2:179596808;179596807;179596806
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-39
• Domain position: 88
• Structural Position: 173
• Q(SASA): 0.3544
• 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
I/T	rs2080640128	None	None	N	0.147	0.164	0.661077055835	gnomAD-4.0.0	2.75152E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.80748E-06	2.34439E-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
I/A	0.1378	likely_benign	0.1336	benign	-1.113	Destabilizing	None	N	0.155	neutral	None	None	None	None	N
I/C	0.5218	ambiguous	0.5526	ambiguous	-0.893	Destabilizing	0.356	N	0.531	neutral	None	None	None	None	N
I/D	0.3954	ambiguous	0.4072	ambiguous	0.04	Stabilizing	0.136	N	0.602	neutral	None	None	None	None	N
I/E	0.3227	likely_benign	0.3374	benign	0.014	Stabilizing	0.072	N	0.587	neutral	None	None	None	None	N
I/F	0.1151	likely_benign	0.1185	benign	-0.859	Destabilizing	None	N	0.153	neutral	N	0.428700238	None	None	N
I/G	0.3959	ambiguous	0.3986	ambiguous	-1.367	Destabilizing	0.016	N	0.47	neutral	None	None	None	None	N
I/H	0.2966	likely_benign	0.3064	benign	-0.628	Destabilizing	0.628	D	0.557	neutral	None	None	None	None	N
I/K	0.1897	likely_benign	0.1988	benign	-0.435	Destabilizing	0.072	N	0.563	neutral	None	None	None	None	N
I/L	0.089	likely_benign	0.0926	benign	-0.524	Destabilizing	None	N	0.077	neutral	N	0.404284583	None	None	N
I/M	0.0725	likely_benign	0.0733	benign	-0.503	Destabilizing	0.171	N	0.481	neutral	N	0.475819395	None	None	N
I/N	0.1536	likely_benign	0.1594	benign	-0.237	Destabilizing	0.106	N	0.632	neutral	N	0.40611138	None	None	N
I/P	0.5652	likely_pathogenic	0.5716	pathogenic	-0.687	Destabilizing	0.136	N	0.628	neutral	None	None	None	None	N
I/Q	0.2501	likely_benign	0.2599	benign	-0.416	Destabilizing	0.356	N	0.62	neutral	None	None	None	None	N
I/R	0.1392	likely_benign	0.1433	benign	None	Stabilizing	0.136	N	0.635	neutral	None	None	None	None	N
I/S	0.1449	likely_benign	0.1472	benign	-0.934	Destabilizing	0.012	N	0.422	neutral	N	0.354719768	None	None	N
I/T	0.083	likely_benign	0.0818	benign	-0.841	Destabilizing	None	N	0.147	neutral	N	0.36968922	None	None	N
I/V	0.0598	likely_benign	0.0607	benign	-0.687	Destabilizing	None	N	0.078	neutral	N	0.411730631	None	None	N
I/W	0.5745	likely_pathogenic	0.6044	pathogenic	-0.846	Destabilizing	0.864	D	0.549	neutral	None	None	None	None	N
I/Y	0.3342	likely_benign	0.3474	ambiguous	-0.581	Destabilizing	0.038	N	0.588	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.