TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20628	62107;62108;62109	chr2:178589843;178589842;178589841	chr2:179454570;179454569;179454568
N2AB	18987	57184;57185;57186	chr2:178589843;178589842;178589841	chr2:179454570;179454569;179454568
N2A	18060	54403;54404;54405	chr2:178589843;178589842;178589841	chr2:179454570;179454569;179454568
N2B	11563	34912;34913;34914	chr2:178589843;178589842;178589841	chr2:179454570;179454569;179454568
Novex-1	11688	35287;35288;35289	chr2:178589843;178589842;178589841	chr2:179454570;179454569;179454568
Novex-2	11755	35488;35489;35490	chr2:178589843;178589842;178589841	chr2:179454570;179454569;179454568
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Fn3-37
• Domain position: 60
• Structural Position: 92
• Q(SASA): 0.152
• 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/V	rs778583635	-0.711	None	N	0.195	0.078	0.316788114976	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	5.6E-05	None	0	None	0	0	0
I/V	rs778583635	-0.711	None	N	0.195	0.078	0.316788114976	gnomAD-4.0.0	1.59194E-06	None	None	None	None	N	None	0	0	None	0	2.77855E-05	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	0.5906	likely_pathogenic	0.6513	pathogenic	-1.896	Destabilizing	0.072	N	0.486	neutral	None	None	None	None	N
I/C	0.7346	likely_pathogenic	0.7302	pathogenic	-1.235	Destabilizing	0.909	D	0.65	neutral	None	None	None	None	N
I/D	0.9384	likely_pathogenic	0.9471	pathogenic	-1.44	Destabilizing	0.726	D	0.709	prob.delet.	None	None	None	None	N
I/E	0.8457	likely_pathogenic	0.8436	pathogenic	-1.289	Destabilizing	0.726	D	0.688	prob.neutral	None	None	None	None	N
I/F	0.2136	likely_benign	0.2241	benign	-1.017	Destabilizing	0.497	N	0.556	neutral	N	0.475749532	None	None	N
I/G	0.8424	likely_pathogenic	0.8783	pathogenic	-2.358	Highly Destabilizing	0.726	D	0.667	neutral	None	None	None	None	N
I/H	0.7608	likely_pathogenic	0.7516	pathogenic	-1.505	Destabilizing	0.968	D	0.776	deleterious	None	None	None	None	N
I/K	0.7526	likely_pathogenic	0.7366	pathogenic	-1.42	Destabilizing	0.726	D	0.694	prob.neutral	None	None	None	None	N
I/L	0.14	likely_benign	0.1677	benign	-0.623	Destabilizing	0.025	N	0.387	neutral	N	0.438980655	None	None	N
I/M	0.1497	likely_benign	0.1632	benign	-0.574	Destabilizing	0.497	N	0.601	neutral	N	0.497239525	None	None	N
I/N	0.5967	likely_pathogenic	0.6432	pathogenic	-1.579	Destabilizing	0.859	D	0.751	deleterious	N	0.484232942	None	None	N
I/P	0.9277	likely_pathogenic	0.9419	pathogenic	-1.021	Destabilizing	0.89	D	0.719	prob.delet.	None	None	None	None	N
I/Q	0.6818	likely_pathogenic	0.6775	pathogenic	-1.517	Destabilizing	0.89	D	0.767	deleterious	None	None	None	None	N
I/R	0.6904	likely_pathogenic	0.6613	pathogenic	-1.056	Destabilizing	0.726	D	0.758	deleterious	None	None	None	None	N
I/S	0.5867	likely_pathogenic	0.6349	pathogenic	-2.297	Highly Destabilizing	0.497	N	0.612	neutral	N	0.484059584	None	None	N
I/T	0.4582	ambiguous	0.5064	ambiguous	-2.0	Highly Destabilizing	0.124	N	0.513	neutral	N	0.398763255	None	None	N
I/V	0.0826	likely_benign	0.1012	benign	-1.021	Destabilizing	None	N	0.195	neutral	N	0.428224944	None	None	N
I/W	0.8932	likely_pathogenic	0.8429	pathogenic	-1.234	Destabilizing	0.968	D	0.785	deleterious	None	None	None	None	N
I/Y	0.6304	likely_pathogenic	0.6186	pathogenic	-0.95	Destabilizing	0.726	D	0.617	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.