TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31341	94246;94247;94248	chr2:178547605;178547604;178547603	chr2:179412332;179412331;179412330
N2AB	29700	89323;89324;89325	chr2:178547605;178547604;178547603	chr2:179412332;179412331;179412330
N2A	28773	86542;86543;86544	chr2:178547605;178547604;178547603	chr2:179412332;179412331;179412330
N2B	22276	67051;67052;67053	chr2:178547605;178547604;178547603	chr2:179412332;179412331;179412330
Novex-1	22401	67426;67427;67428	chr2:178547605;178547604;178547603	chr2:179412332;179412331;179412330
Novex-2	22468	67627;67628;67629	chr2:178547605;178547604;178547603	chr2:179412332;179412331;179412330
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-116
• Domain position: 34
• Structural Position: 35
• Q(SASA): 0.1833
• 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
I/M	None	None	1.0	D	0.817	0.493	0.505885190548	gnomAD-4.0.0	1.59112E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85801E-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
I/A	0.9293	likely_pathogenic	0.907	pathogenic	-2.251	Highly Destabilizing	0.999	D	0.675	neutral	None	None	None	None	I
I/C	0.9393	likely_pathogenic	0.9173	pathogenic	-1.644	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	I
I/D	0.9902	likely_pathogenic	0.9858	pathogenic	-2.186	Highly Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	I
I/E	0.9744	likely_pathogenic	0.9676	pathogenic	-2.121	Highly Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	I
I/F	0.8023	likely_pathogenic	0.7297	pathogenic	-1.625	Destabilizing	1.0	D	0.843	deleterious	D	0.533424366	None	None	I
I/G	0.983	likely_pathogenic	0.9748	pathogenic	-2.642	Highly Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	I
I/H	0.9811	likely_pathogenic	0.9719	pathogenic	-1.856	Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	I
I/K	0.9556	likely_pathogenic	0.9398	pathogenic	-1.557	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	I
I/L	0.3344	likely_benign	0.283	benign	-1.2	Destabilizing	0.993	D	0.435	neutral	N	0.471856672	None	None	I
I/M	0.3325	likely_benign	0.28	benign	-1.035	Destabilizing	1.0	D	0.817	deleterious	D	0.524602956	None	None	I
I/N	0.8392	likely_pathogenic	0.809	pathogenic	-1.542	Destabilizing	1.0	D	0.881	deleterious	D	0.536973219	None	None	I
I/P	0.907	likely_pathogenic	0.8982	pathogenic	-1.524	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	I
I/Q	0.967	likely_pathogenic	0.9535	pathogenic	-1.696	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	I
I/R	0.9535	likely_pathogenic	0.9373	pathogenic	-0.975	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	I
I/S	0.9327	likely_pathogenic	0.9121	pathogenic	-2.206	Highly Destabilizing	1.0	D	0.868	deleterious	D	0.536212751	None	None	I
I/T	0.8462	likely_pathogenic	0.8122	pathogenic	-2.019	Highly Destabilizing	1.0	D	0.834	deleterious	N	0.504283428	None	None	I
I/V	0.121	likely_benign	0.1113	benign	-1.524	Destabilizing	0.993	D	0.417	neutral	N	0.459225428	None	None	I
I/W	0.9904	likely_pathogenic	0.9835	pathogenic	-1.765	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	I
I/Y	0.9545	likely_pathogenic	0.9373	pathogenic	-1.532	Destabilizing	1.0	D	0.849	deleterious	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.