TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7250	21973;21974;21975	chr2:178723259;178723258;178723257	chr2:179587986;179587985;179587984
N2AB	6933	21022;21023;21024	chr2:178723259;178723258;178723257	chr2:179587986;179587985;179587984
N2A	6006	18241;18242;18243	chr2:178723259;178723258;178723257	chr2:179587986;179587985;179587984
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: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-57
• Domain position: 21
• Structural Position: 31
• Q(SASA): 0.5609
• 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/G	rs758430575	-1.037	0.998	N	0.635	0.516	0.55563304408	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
E/G	rs758430575	-1.037	0.998	N	0.635	0.516	0.55563304408	gnomAD-4.0.0	1.59181E-06	None	None	None	None	I	None	0	2.28739E-05	None	0	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
E/A	0.5251	ambiguous	0.5686	pathogenic	-0.805	Destabilizing	0.989	D	0.586	neutral	N	0.493823539	None	None	I
E/C	0.9793	likely_pathogenic	0.9819	pathogenic	-0.392	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	I
E/D	0.6576	likely_pathogenic	0.6935	pathogenic	-0.938	Destabilizing	0.994	D	0.537	neutral	N	0.491519361	None	None	I
E/F	0.9684	likely_pathogenic	0.9748	pathogenic	-0.3	Destabilizing	0.995	D	0.719	prob.delet.	None	None	None	None	I
E/G	0.6276	likely_pathogenic	0.6656	pathogenic	-1.141	Destabilizing	0.998	D	0.635	neutral	N	0.509663296	None	None	I
E/H	0.8513	likely_pathogenic	0.8705	pathogenic	-0.483	Destabilizing	0.999	D	0.618	neutral	None	None	None	None	I
E/I	0.8323	likely_pathogenic	0.8746	pathogenic	0.098	Stabilizing	0.999	D	0.721	prob.delet.	None	None	None	None	I
E/K	0.5214	ambiguous	0.583	pathogenic	-0.378	Destabilizing	0.978	D	0.551	neutral	N	0.513414991	None	None	I
E/L	0.876	likely_pathogenic	0.9028	pathogenic	0.098	Stabilizing	0.998	D	0.653	neutral	None	None	None	None	I
E/M	0.8665	likely_pathogenic	0.8941	pathogenic	0.459	Stabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	I
E/N	0.7961	likely_pathogenic	0.8174	pathogenic	-0.867	Destabilizing	0.999	D	0.593	neutral	None	None	None	None	I
E/P	0.9881	likely_pathogenic	0.9871	pathogenic	-0.182	Destabilizing	1.0	D	0.704	prob.neutral	None	None	None	None	I
E/Q	0.2885	likely_benign	0.3157	benign	-0.758	Destabilizing	0.889	D	0.422	neutral	N	0.490189461	None	None	I
E/R	0.6886	likely_pathogenic	0.7214	pathogenic	-0.105	Destabilizing	0.998	D	0.595	neutral	None	None	None	None	I
E/S	0.6112	likely_pathogenic	0.6396	pathogenic	-1.13	Destabilizing	0.992	D	0.559	neutral	None	None	None	None	I
E/T	0.6404	likely_pathogenic	0.6854	pathogenic	-0.851	Destabilizing	0.999	D	0.671	neutral	None	None	None	None	I
E/V	0.6126	likely_pathogenic	0.6807	pathogenic	-0.182	Destabilizing	0.997	D	0.636	neutral	D	0.538486794	None	None	I
E/W	0.9898	likely_pathogenic	0.9921	pathogenic	-0.032	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	I
E/Y	0.9392	likely_pathogenic	0.9521	pathogenic	-0.04	Destabilizing	0.784	D	0.477	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.