TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16583	49972;49973;49974	chr2:178612974;178612973;178612972	chr2:179477701;179477700;179477699
N2AB	14942	45049;45050;45051	chr2:178612974;178612973;178612972	chr2:179477701;179477700;179477699
N2A	14015	42268;42269;42270	chr2:178612974;178612973;178612972	chr2:179477701;179477700;179477699
N2B	7518	22777;22778;22779	chr2:178612974;178612973;178612972	chr2:179477701;179477700;179477699
Novex-1	7643	23152;23153;23154	chr2:178612974;178612973;178612972	chr2:179477701;179477700;179477699
Novex-2	7710	23353;23354;23355	chr2:178612974;178612973;178612972	chr2:179477701;179477700;179477699
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: Fn3-8
• Domain position: 33
• Structural Position: 35
• Q(SASA): 0.1842
• 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	rs372866841	-2.18	0.645	D	0.773	0.481	None	gnomAD-2.1.1	7.16E-06	None	None	None	None	N	None	8.27E-05	0	None	0	0	None	0	None	0	0	0
I/T	rs372866841	-2.18	0.645	D	0.773	0.481	None	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
I/T	rs372866841	-2.18	0.645	D	0.773	0.481	None	gnomAD-4.0.0	6.20118E-06	None	None	None	None	N	None	2.6728E-05	0	None	0	0	None	0	0	5.93599E-06	1.09827E-05	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	0.8841	likely_pathogenic	0.9426	pathogenic	-2.479	Highly Destabilizing	0.547	D	0.669	neutral	None	None	None	None	N
I/C	0.9771	likely_pathogenic	0.9871	pathogenic	-1.605	Destabilizing	0.985	D	0.734	prob.delet.	None	None	None	None	N
I/D	0.9951	likely_pathogenic	0.9982	pathogenic	-2.505	Highly Destabilizing	0.945	D	0.84	deleterious	None	None	None	None	N
I/E	0.9802	likely_pathogenic	0.9926	pathogenic	-2.403	Highly Destabilizing	0.945	D	0.835	deleterious	None	None	None	None	N
I/F	0.8289	likely_pathogenic	0.9139	pathogenic	-1.618	Destabilizing	0.864	D	0.751	deleterious	D	0.676033394	None	None	N
I/G	0.9849	likely_pathogenic	0.9938	pathogenic	-2.922	Highly Destabilizing	0.945	D	0.834	deleterious	None	None	None	None	N
I/H	0.9918	likely_pathogenic	0.9969	pathogenic	-2.215	Highly Destabilizing	0.995	D	0.795	deleterious	None	None	None	None	N
I/K	0.9757	likely_pathogenic	0.9914	pathogenic	-1.907	Destabilizing	0.945	D	0.833	deleterious	None	None	None	None	N
I/L	0.4034	ambiguous	0.4176	ambiguous	-1.25	Destabilizing	0.141	N	0.429	neutral	N	0.508024661	None	None	N
I/M	0.3687	ambiguous	0.4657	ambiguous	-0.965	Destabilizing	0.864	D	0.715	prob.delet.	D	0.695956131	None	None	N
I/N	0.9398	likely_pathogenic	0.9622	pathogenic	-1.886	Destabilizing	0.975	D	0.835	deleterious	D	0.659865613	None	None	N
I/P	0.9225	likely_pathogenic	0.9613	pathogenic	-1.636	Destabilizing	0.981	D	0.841	deleterious	None	None	None	None	N
I/Q	0.9776	likely_pathogenic	0.9917	pathogenic	-1.963	Destabilizing	0.981	D	0.829	deleterious	None	None	None	None	N
I/R	0.9651	likely_pathogenic	0.9882	pathogenic	-1.335	Destabilizing	0.945	D	0.834	deleterious	None	None	None	None	N
I/S	0.9379	likely_pathogenic	0.9729	pathogenic	-2.537	Highly Destabilizing	0.864	D	0.813	deleterious	D	0.718884754	None	None	N
I/T	0.6986	likely_pathogenic	0.8433	pathogenic	-2.312	Highly Destabilizing	0.645	D	0.773	deleterious	D	0.649702377	None	None	N
I/V	0.1343	likely_benign	0.1404	benign	-1.636	Destabilizing	0.002	N	0.238	neutral	N	0.483782619	None	None	N
I/W	0.9902	likely_pathogenic	0.9966	pathogenic	-1.864	Destabilizing	0.995	D	0.746	deleterious	None	None	None	None	N
I/Y	0.9738	likely_pathogenic	0.989	pathogenic	-1.662	Destabilizing	0.945	D	0.784	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.