TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20736	62431;62432;62433	chr2:178589519;178589518;178589517	chr2:179454246;179454245;179454244
N2AB	19095	57508;57509;57510	chr2:178589519;178589518;178589517	chr2:179454246;179454245;179454244
N2A	18168	54727;54728;54729	chr2:178589519;178589518;178589517	chr2:179454246;179454245;179454244
N2B	11671	35236;35237;35238	chr2:178589519;178589518;178589517	chr2:179454246;179454245;179454244
Novex-1	11796	35611;35612;35613	chr2:178589519;178589518;178589517	chr2:179454246;179454245;179454244
Novex-2	11863	35812;35813;35814	chr2:178589519;178589518;178589517	chr2:179454246;179454245;179454244
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Fn3-38
• Domain position: 69
• Structural Position: 100
• Q(SASA): 0.6772
• 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
N/Y	None	None	1.0	N	0.805	0.49	0.617691798299	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05

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
N/A	0.7836	likely_pathogenic	0.7773	pathogenic	-0.377	Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	N
N/C	0.8137	likely_pathogenic	0.8528	pathogenic	0.243	Stabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
N/D	0.3243	likely_benign	0.2908	benign	0.087	Stabilizing	0.999	D	0.715	prob.delet.	N	0.48981212	None	None	N
N/E	0.7443	likely_pathogenic	0.7378	pathogenic	0.084	Stabilizing	0.999	D	0.796	deleterious	None	None	None	None	N
N/F	0.8997	likely_pathogenic	0.927	pathogenic	-0.51	Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	N
N/G	0.4343	ambiguous	0.4298	ambiguous	-0.603	Destabilizing	0.999	D	0.647	neutral	None	None	None	None	N
N/H	0.2856	likely_benign	0.3118	benign	-0.518	Destabilizing	1.0	D	0.797	deleterious	N	0.502992061	None	None	N
N/I	0.9219	likely_pathogenic	0.92	pathogenic	0.143	Stabilizing	1.0	D	0.82	deleterious	N	0.492146066	None	None	N
N/K	0.7173	likely_pathogenic	0.6941	pathogenic	-0.021	Destabilizing	1.0	D	0.807	deleterious	N	0.512862338	None	None	N
N/L	0.7733	likely_pathogenic	0.762	pathogenic	0.143	Stabilizing	1.0	D	0.794	deleterious	None	None	None	None	N
N/M	0.7845	likely_pathogenic	0.8011	pathogenic	0.396	Stabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
N/P	0.9827	likely_pathogenic	0.9882	pathogenic	-0.002	Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	N
N/Q	0.6786	likely_pathogenic	0.6923	pathogenic	-0.477	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
N/R	0.8053	likely_pathogenic	0.8047	pathogenic	0.025	Stabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
N/S	0.2924	likely_benign	0.287	benign	-0.32	Destabilizing	0.999	D	0.653	neutral	N	0.521327106	None	None	N
N/T	0.6374	likely_pathogenic	0.6094	pathogenic	-0.168	Destabilizing	0.999	D	0.799	deleterious	N	0.479864708	None	None	N
N/V	0.9119	likely_pathogenic	0.9116	pathogenic	-0.002	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
N/W	0.9465	likely_pathogenic	0.9658	pathogenic	-0.419	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
N/Y	0.4471	ambiguous	0.511	ambiguous	-0.189	Destabilizing	1.0	D	0.805	deleterious	N	0.467494444	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.