TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26522	79789;79790;79791	chr2:178566568;178566567;178566566	chr2:179431295;179431294;179431293
N2AB	24881	74866;74867;74868	chr2:178566568;178566567;178566566	chr2:179431295;179431294;179431293
N2A	23954	72085;72086;72087	chr2:178566568;178566567;178566566	chr2:179431295;179431294;179431293
N2B	17457	52594;52595;52596	chr2:178566568;178566567;178566566	chr2:179431295;179431294;179431293
Novex-1	17582	52969;52970;52971	chr2:178566568;178566567;178566566	chr2:179431295;179431294;179431293
Novex-2	17649	53170;53171;53172	chr2:178566568;178566567;178566566	chr2:179431295;179431294;179431293
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-81
• Domain position: 36
• Structural Position: 38
• Q(SASA): 0.0846
• 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
Y/C	None	None	1.0	D	0.827	0.836	0.821884243264	gnomAD-4.0.0	1.59299E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85874E-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
Y/A	0.9928	likely_pathogenic	0.9921	pathogenic	-3.396	Highly Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
Y/C	0.8533	likely_pathogenic	0.8251	pathogenic	-1.855	Destabilizing	1.0	D	0.827	deleterious	D	0.653678792	None	None	N
Y/D	0.9931	likely_pathogenic	0.9929	pathogenic	-3.784	Highly Destabilizing	1.0	D	0.855	deleterious	D	0.653880596	None	None	N
Y/E	0.998	likely_pathogenic	0.9981	pathogenic	-3.563	Highly Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
Y/F	0.2553	likely_benign	0.2512	benign	-1.306	Destabilizing	0.999	D	0.646	neutral	D	0.532485401	None	None	N
Y/G	0.9836	likely_pathogenic	0.984	pathogenic	-3.812	Highly Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
Y/H	0.959	likely_pathogenic	0.959	pathogenic	-2.481	Highly Destabilizing	1.0	D	0.806	deleterious	D	0.653476988	None	None	N
Y/I	0.9663	likely_pathogenic	0.963	pathogenic	-1.988	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
Y/K	0.9979	likely_pathogenic	0.998	pathogenic	-2.438	Highly Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
Y/L	0.942	likely_pathogenic	0.9397	pathogenic	-1.988	Destabilizing	0.999	D	0.681	prob.neutral	None	None	None	None	N
Y/M	0.9724	likely_pathogenic	0.9695	pathogenic	-1.69	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
Y/N	0.9481	likely_pathogenic	0.947	pathogenic	-3.261	Highly Destabilizing	1.0	D	0.835	deleterious	D	0.653880596	None	None	N
Y/P	0.9987	likely_pathogenic	0.9988	pathogenic	-2.476	Highly Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	N
Y/Q	0.9969	likely_pathogenic	0.9968	pathogenic	-2.984	Highly Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
Y/R	0.9929	likely_pathogenic	0.993	pathogenic	-2.233	Highly Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
Y/S	0.9713	likely_pathogenic	0.9681	pathogenic	-3.564	Highly Destabilizing	1.0	D	0.833	deleterious	D	0.653880596	None	None	N
Y/T	0.99	likely_pathogenic	0.9891	pathogenic	-3.223	Highly Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
Y/V	0.9408	likely_pathogenic	0.9334	pathogenic	-2.476	Highly Destabilizing	1.0	D	0.698	prob.neutral	None	None	None	None	N
Y/W	0.8284	likely_pathogenic	0.8053	pathogenic	-0.54	Destabilizing	1.0	D	0.805	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.