TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21081	63466;63467;63468	chr2:178588166;178588165;178588164	chr2:179452893;179452892;179452891
N2AB	19440	58543;58544;58545	chr2:178588166;178588165;178588164	chr2:179452893;179452892;179452891
N2A	18513	55762;55763;55764	chr2:178588166;178588165;178588164	chr2:179452893;179452892;179452891
N2B	12016	36271;36272;36273	chr2:178588166;178588165;178588164	chr2:179452893;179452892;179452891
Novex-1	12141	36646;36647;36648	chr2:178588166;178588165;178588164	chr2:179452893;179452892;179452891
Novex-2	12208	36847;36848;36849	chr2:178588166;178588165;178588164	chr2:179452893;179452892;179452891
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Fn3-41
• Domain position: 18
• Structural Position: 20
• Q(SASA): 0.0642
• 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	None	None	0.722	N	0.808	0.48	0.580021155531	gnomAD-4.0.0	6.88023E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.04347E-07	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
I/A	0.8009	likely_pathogenic	0.7635	pathogenic	-3.019	Highly Destabilizing	0.415	N	0.738	prob.delet.	None	None	None	None	N
I/C	0.9059	likely_pathogenic	0.8861	pathogenic	-3.017	Highly Destabilizing	0.996	D	0.764	deleterious	None	None	None	None	N
I/D	0.9988	likely_pathogenic	0.9981	pathogenic	-3.518	Highly Destabilizing	0.987	D	0.828	deleterious	None	None	None	None	N
I/E	0.9956	likely_pathogenic	0.9935	pathogenic	-3.231	Highly Destabilizing	0.961	D	0.832	deleterious	None	None	None	None	N
I/F	0.7263	likely_pathogenic	0.7171	pathogenic	-1.941	Destabilizing	0.923	D	0.721	prob.delet.	None	None	None	None	N
I/G	0.9872	likely_pathogenic	0.9827	pathogenic	-3.609	Highly Destabilizing	0.961	D	0.824	deleterious	None	None	None	None	N
I/H	0.9934	likely_pathogenic	0.9914	pathogenic	-3.115	Highly Destabilizing	0.996	D	0.799	deleterious	None	None	None	None	N
I/K	0.9908	likely_pathogenic	0.9873	pathogenic	-2.403	Highly Destabilizing	0.949	D	0.831	deleterious	N	0.499919702	None	None	N
I/L	0.3267	likely_benign	0.2884	benign	-1.262	Destabilizing	0.003	N	0.271	neutral	N	0.477679824	None	None	N
I/M	0.3207	likely_benign	0.2726	benign	-1.697	Destabilizing	0.901	D	0.663	neutral	N	0.500636829	None	None	N
I/N	0.9781	likely_pathogenic	0.971	pathogenic	-3.0	Highly Destabilizing	0.987	D	0.824	deleterious	None	None	None	None	N
I/P	0.9971	likely_pathogenic	0.997	pathogenic	-1.836	Destabilizing	0.987	D	0.819	deleterious	None	None	None	None	N
I/Q	0.9903	likely_pathogenic	0.9859	pathogenic	-2.749	Highly Destabilizing	0.987	D	0.837	deleterious	None	None	None	None	N
I/R	0.9825	likely_pathogenic	0.9773	pathogenic	-2.246	Highly Destabilizing	0.949	D	0.821	deleterious	N	0.488563397	None	None	N
I/S	0.9385	likely_pathogenic	0.9201	pathogenic	-3.714	Highly Destabilizing	0.923	D	0.784	deleterious	None	None	None	None	N
I/T	0.9025	likely_pathogenic	0.8835	pathogenic	-3.258	Highly Destabilizing	0.722	D	0.808	deleterious	N	0.481308468	None	None	N
I/V	0.0824	likely_benign	0.0819	benign	-1.836	Destabilizing	0.003	N	0.203	neutral	N	0.376166036	None	None	N
I/W	0.9957	likely_pathogenic	0.995	pathogenic	-2.239	Highly Destabilizing	0.996	D	0.786	deleterious	None	None	None	None	N
I/Y	0.9717	likely_pathogenic	0.9669	pathogenic	-2.06	Highly Destabilizing	0.961	D	0.807	deleterious	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.