TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5152	15679;15680;15681	chr2:178734370;178734369;178734368	chr2:179599097;179599096;179599095
N2AB	4835	14728;14729;14730	chr2:178734370;178734369;178734368	chr2:179599097;179599096;179599095
N2A	3908	11947;11948;11949	chr2:178734370;178734369;178734368	chr2:179599097;179599096;179599095
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: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-34
• Domain position: 78
• Structural Position: 162
• Q(SASA): 0.979
• 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
E/K	None	None	0.978	N	0.541	0.38	0.455996456696	gnomAD-4.0.0	6.86655E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.16902E-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	0.2932	likely_benign	0.2842	benign	-0.038	Destabilizing	0.989	D	0.54	neutral	N	0.516109536	None	None	I
E/C	0.96	likely_pathogenic	0.9622	pathogenic	-0.146	Destabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	I
E/D	0.1305	likely_benign	0.1273	benign	-0.378	Destabilizing	0.054	N	0.402	neutral	N	0.485681447	None	None	I
E/F	0.9413	likely_pathogenic	0.9368	pathogenic	-0.109	Destabilizing	1.0	D	0.639	neutral	None	None	None	None	I
E/G	0.3608	ambiguous	0.3582	ambiguous	-0.147	Destabilizing	0.978	D	0.451	neutral	N	0.505596981	None	None	I
E/H	0.755	likely_pathogenic	0.7419	pathogenic	0.458	Stabilizing	1.0	D	0.589	neutral	None	None	None	None	I
E/I	0.6284	likely_pathogenic	0.6437	pathogenic	0.189	Stabilizing	0.999	D	0.644	neutral	None	None	None	None	I
E/K	0.3815	ambiguous	0.3437	ambiguous	0.428	Stabilizing	0.978	D	0.541	neutral	N	0.511986766	None	None	I
E/L	0.7301	likely_pathogenic	0.7282	pathogenic	0.189	Stabilizing	0.998	D	0.625	neutral	None	None	None	None	I
E/M	0.7492	likely_pathogenic	0.7522	pathogenic	0.01	Stabilizing	1.0	D	0.609	neutral	None	None	None	None	I
E/N	0.4513	ambiguous	0.4453	ambiguous	0.186	Stabilizing	0.995	D	0.554	neutral	None	None	None	None	I
E/P	0.7473	likely_pathogenic	0.7228	pathogenic	0.131	Stabilizing	0.999	D	0.555	neutral	None	None	None	None	I
E/Q	0.3255	likely_benign	0.3099	benign	0.19	Stabilizing	0.997	D	0.531	neutral	N	0.506414122	None	None	I
E/R	0.5818	likely_pathogenic	0.5358	ambiguous	0.623	Stabilizing	0.998	D	0.595	neutral	None	None	None	None	I
E/S	0.3662	ambiguous	0.3377	benign	0.066	Stabilizing	0.983	D	0.534	neutral	None	None	None	None	I
E/T	0.4342	ambiguous	0.4323	ambiguous	0.162	Stabilizing	0.998	D	0.524	neutral	None	None	None	None	I
E/V	0.4161	ambiguous	0.4243	ambiguous	0.131	Stabilizing	0.999	D	0.575	neutral	N	0.513746398	None	None	I
E/W	0.9802	likely_pathogenic	0.9779	pathogenic	-0.071	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	I
E/Y	0.8741	likely_pathogenic	0.8667	pathogenic	0.111	Stabilizing	1.0	D	0.595	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.