TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6559	19900;19901;19902	chr2:178728149;178728148;178728147	chr2:179592876;179592875;179592874
N2AB	6242	18949;18950;18951	chr2:178728149;178728148;178728147	chr2:179592876;179592875;179592874
N2A	5315	16168;16169;16170	chr2:178728149;178728148;178728147	chr2:179592876;179592875;179592874
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: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-49
• Domain position: 79
• Structural Position: 163
• Q(SASA): 0.5838
• 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/P	None	None	0.056	D	0.441	0.475	0.416833835346	gnomAD-4.0.0	1.61547E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.05998E-05

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	0.6841	likely_pathogenic	0.7057	pathogenic	-0.899	Destabilizing	0.999	D	0.595	neutral	None	None	None	None	I
A/D	0.6552	likely_pathogenic	0.637	pathogenic	-0.635	Destabilizing	0.975	D	0.643	neutral	None	None	None	None	I
A/E	0.5615	ambiguous	0.5454	ambiguous	-0.785	Destabilizing	0.967	D	0.537	neutral	N	0.511309137	None	None	I
A/F	0.3712	ambiguous	0.4317	ambiguous	-0.957	Destabilizing	0.073	N	0.545	neutral	None	None	None	None	I
A/G	0.2871	likely_benign	0.3081	benign	-0.29	Destabilizing	0.892	D	0.52	neutral	D	0.525018846	None	None	I
A/H	0.7063	likely_pathogenic	0.7486	pathogenic	-0.221	Destabilizing	0.999	D	0.667	neutral	None	None	None	None	I
A/I	0.3403	ambiguous	0.3562	ambiguous	-0.469	Destabilizing	0.975	D	0.566	neutral	None	None	None	None	I
A/K	0.7883	likely_pathogenic	0.7946	pathogenic	-0.624	Destabilizing	0.975	D	0.546	neutral	None	None	None	None	I
A/L	0.2871	likely_benign	0.2966	benign	-0.469	Destabilizing	0.845	D	0.551	neutral	None	None	None	None	I
A/M	0.3503	ambiguous	0.3865	ambiguous	-0.622	Destabilizing	0.999	D	0.591	neutral	None	None	None	None	I
A/N	0.5895	likely_pathogenic	0.6055	pathogenic	-0.338	Destabilizing	0.987	D	0.657	neutral	None	None	None	None	I
A/P	0.8728	likely_pathogenic	0.8519	pathogenic	-0.383	Destabilizing	0.056	N	0.441	neutral	D	0.538567652	None	None	I
A/Q	0.6112	likely_pathogenic	0.6387	pathogenic	-0.611	Destabilizing	0.987	D	0.581	neutral	None	None	None	None	I
A/R	0.6639	likely_pathogenic	0.6756	pathogenic	-0.152	Destabilizing	0.987	D	0.573	neutral	None	None	None	None	I
A/S	0.144	likely_benign	0.1532	benign	-0.518	Destabilizing	0.892	D	0.541	neutral	D	0.522043105	None	None	I
A/T	0.1732	likely_benign	0.1822	benign	-0.598	Destabilizing	0.892	D	0.529	neutral	N	0.521282636	None	None	I
A/V	0.138	likely_benign	0.1484	benign	-0.383	Destabilizing	0.892	D	0.537	neutral	N	0.487262946	None	None	I
A/W	0.8537	likely_pathogenic	0.8667	pathogenic	-1.043	Destabilizing	0.999	D	0.727	prob.delet.	None	None	None	None	I
A/Y	0.6498	likely_pathogenic	0.6934	pathogenic	-0.74	Destabilizing	0.95	D	0.654	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.