TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19917	59974;59975;59976	chr2:178592155;178592154;178592153	chr2:179456882;179456881;179456880
N2AB	18276	55051;55052;55053	chr2:178592155;178592154;178592153	chr2:179456882;179456881;179456880
N2A	17349	52270;52271;52272	chr2:178592155;178592154;178592153	chr2:179456882;179456881;179456880
N2B	10852	32779;32780;32781	chr2:178592155;178592154;178592153	chr2:179456882;179456881;179456880
Novex-1	10977	33154;33155;33156	chr2:178592155;178592154;178592153	chr2:179456882;179456881;179456880
Novex-2	11044	33355;33356;33357	chr2:178592155;178592154;178592153	chr2:179456882;179456881;179456880
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Fn3-32
• Domain position: 41
• Structural Position: 43
• Q(SASA): 0.1631
• 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
R/T	None	None	0.117	D	0.467	0.162	0.215869574891	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
R/A	0.704	likely_pathogenic	0.6782	pathogenic	-2.046	Highly Destabilizing	0.035	N	0.455	neutral	None	None	None	None	N
R/C	0.2559	likely_benign	0.2286	benign	-1.961	Destabilizing	0.935	D	0.64	neutral	None	None	None	None	N
R/D	0.9596	likely_pathogenic	0.9563	pathogenic	-0.848	Destabilizing	0.149	N	0.573	neutral	None	None	None	None	N
R/E	0.6728	likely_pathogenic	0.6595	pathogenic	-0.657	Destabilizing	0.035	N	0.471	neutral	None	None	None	None	N
R/F	0.7461	likely_pathogenic	0.7425	pathogenic	-1.477	Destabilizing	0.791	D	0.624	neutral	None	None	None	None	N
R/G	0.5829	likely_pathogenic	0.5694	pathogenic	-2.362	Highly Destabilizing	0.117	N	0.513	neutral	N	0.47325857	None	None	N
R/H	0.2207	likely_benign	0.2148	benign	-2.268	Highly Destabilizing	0.555	D	0.447	neutral	None	None	None	None	N
R/I	0.6089	likely_pathogenic	0.5887	pathogenic	-1.137	Destabilizing	0.484	N	0.625	neutral	N	0.47300508	None	None	N
R/K	0.0735	likely_benign	0.0658	benign	-1.424	Destabilizing	None	N	0.151	neutral	N	0.405214798	None	None	N
R/L	0.3926	ambiguous	0.352	ambiguous	-1.137	Destabilizing	0.149	N	0.513	neutral	None	None	None	None	N
R/M	0.3662	ambiguous	0.3446	ambiguous	-1.578	Destabilizing	0.791	D	0.535	neutral	None	None	None	None	N
R/N	0.8546	likely_pathogenic	0.8446	pathogenic	-1.193	Destabilizing	0.149	N	0.438	neutral	None	None	None	None	N
R/P	0.9838	likely_pathogenic	0.9828	pathogenic	-1.429	Destabilizing	0.555	D	0.589	neutral	None	None	None	None	N
R/Q	0.1443	likely_benign	0.1429	benign	-1.189	Destabilizing	0.081	N	0.464	neutral	None	None	None	None	N
R/S	0.8192	likely_pathogenic	0.8083	pathogenic	-2.158	Highly Destabilizing	0.062	N	0.453	neutral	N	0.490678912	None	None	N
R/T	0.6818	likely_pathogenic	0.6738	pathogenic	-1.768	Destabilizing	0.117	N	0.467	neutral	D	0.526082352	None	None	N
R/V	0.6846	likely_pathogenic	0.642	pathogenic	-1.429	Destabilizing	0.38	N	0.597	neutral	None	None	None	None	N
R/W	0.3719	ambiguous	0.3936	ambiguous	-0.973	Destabilizing	0.935	D	0.673	neutral	None	None	None	None	N
R/Y	0.6049	likely_pathogenic	0.6168	pathogenic	-0.807	Destabilizing	0.555	D	0.599	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.