TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6146	18661;18662;18663	chr2:178729817;178729816;178729815	chr2:179594544;179594543;179594542
N2AB	5829	17710;17711;17712	chr2:178729817;178729816;178729815	chr2:179594544;179594543;179594542
N2A	4902	14929;14930;14931	chr2:178729817;178729816;178729815	chr2:179594544;179594543;179594542
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: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Ig-45
• Domain position: 42
• Structural Position: 58
• Q(SASA): 0.1471
• 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	rs1578142340	None	0.722	D	0.551	0.561	0.773736090878	gnomAD-4.0.0	1.36851E-06	None	None	None	None	N	None	2.98864E-05	0	None	0	0	None	0	0	0	0	1.65678E-05
I/V	rs2080073128	None	0.003	D	0.209	0.119	0.520110530135	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
I/V	rs2080073128	None	0.003	D	0.209	0.119	0.520110530135	gnomAD-4.0.0	6.57065E-06	None	None	None	None	N	None	2.41161E-05	0	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
I/A	0.5167	ambiguous	0.5347	ambiguous	-2.29	Highly Destabilizing	0.415	N	0.535	neutral	None	None	None	None	N
I/C	0.7928	likely_pathogenic	0.7993	pathogenic	-1.437	Destabilizing	0.996	D	0.627	neutral	None	None	None	None	N
I/D	0.7618	likely_pathogenic	0.7682	pathogenic	-2.427	Highly Destabilizing	0.987	D	0.702	prob.neutral	None	None	None	None	N
I/E	0.6731	likely_pathogenic	0.6866	pathogenic	-2.187	Highly Destabilizing	0.961	D	0.689	prob.neutral	None	None	None	None	N
I/F	0.1903	likely_benign	0.1926	benign	-1.405	Destabilizing	0.923	D	0.527	neutral	None	None	None	None	N
I/G	0.777	likely_pathogenic	0.7959	pathogenic	-2.82	Highly Destabilizing	0.961	D	0.66	neutral	None	None	None	None	N
I/H	0.6812	likely_pathogenic	0.6916	pathogenic	-2.19	Highly Destabilizing	0.996	D	0.711	prob.delet.	None	None	None	None	N
I/K	0.5408	ambiguous	0.5507	ambiguous	-1.629	Destabilizing	0.949	D	0.693	prob.neutral	D	0.559344933	None	None	N
I/L	0.1123	likely_benign	0.1167	benign	-0.755	Destabilizing	0.19	N	0.377	neutral	N	0.458633569	None	None	N
I/M	0.1024	likely_benign	0.1037	benign	-0.673	Destabilizing	0.901	D	0.549	neutral	N	0.512741169	None	None	N
I/N	0.3778	ambiguous	0.3871	ambiguous	-1.986	Destabilizing	0.987	D	0.729	prob.delet.	None	None	None	None	N
I/P	0.8342	likely_pathogenic	0.8589	pathogenic	-1.249	Destabilizing	0.987	D	0.723	prob.delet.	None	None	None	None	N
I/Q	0.6048	likely_pathogenic	0.6184	pathogenic	-1.819	Destabilizing	0.987	D	0.729	prob.delet.	None	None	None	None	N
I/R	0.4834	ambiguous	0.4906	ambiguous	-1.484	Destabilizing	0.949	D	0.73	prob.delet.	D	0.541240678	None	None	N
I/S	0.5323	ambiguous	0.5484	ambiguous	-2.674	Highly Destabilizing	0.923	D	0.623	neutral	None	None	None	None	N
I/T	0.5162	ambiguous	0.6129	pathogenic	-2.276	Highly Destabilizing	0.722	D	0.551	neutral	D	0.538198804	None	None	N
I/V	0.0904	likely_benign	0.0935	benign	-1.249	Destabilizing	0.003	N	0.209	neutral	D	0.524632062	None	None	N
I/W	0.7858	likely_pathogenic	0.7963	pathogenic	-1.715	Destabilizing	0.996	D	0.709	prob.delet.	None	None	None	None	N
I/Y	0.5315	ambiguous	0.5287	ambiguous	-1.397	Destabilizing	0.961	D	0.648	neutral	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.