TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13946	42061;42062;42063	chr2:178635488;178635487;178635486	chr2:179500215;179500214;179500213
N2AB	12305	37138;37139;37140	chr2:178635488;178635487;178635486	chr2:179500215;179500214;179500213
N2A	11378	34357;34358;34359	chr2:178635488;178635487;178635486	chr2:179500215;179500214;179500213
N2B	4881	14866;14867;14868	chr2:178635488;178635487;178635486	chr2:179500215;179500214;179500213
Novex-1	5006	15241;15242;15243	chr2:178635488;178635487;178635486	chr2:179500215;179500214;179500213
Novex-2	5073	15442;15443;15444	chr2:178635488;178635487;178635486	chr2:179500215;179500214;179500213
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-89
• Domain position: 71
• Structural Position: 155
• Q(SASA): 0.1771
• 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
A/T	None	None	0.028	N	0.37	0.085	0.0954503805726	gnomAD-4.0.0	6.88053E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.6645E-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
A/C	0.7362	likely_pathogenic	0.6192	pathogenic	-0.664	Destabilizing	0.996	D	0.701	prob.delet.	None	None	None	None	N
A/D	0.9727	likely_pathogenic	0.9288	pathogenic	-2.34	Highly Destabilizing	0.909	D	0.736	deleterious	None	None	None	None	N
A/E	0.954	likely_pathogenic	0.8766	pathogenic	-2.045	Highly Destabilizing	0.883	D	0.735	deleterious	N	0.428274213	None	None	N
A/F	0.883	likely_pathogenic	0.7541	pathogenic	-0.575	Destabilizing	0.953	D	0.782	deleterious	None	None	None	None	N
A/G	0.4343	ambiguous	0.3538	ambiguous	-1.707	Destabilizing	0.518	D	0.591	neutral	N	0.432051466	None	None	N
A/H	0.9603	likely_pathogenic	0.8977	pathogenic	-2.09	Highly Destabilizing	0.987	D	0.753	deleterious	None	None	None	None	N
A/I	0.886	likely_pathogenic	0.7033	pathogenic	0.245	Stabilizing	0.909	D	0.753	deleterious	None	None	None	None	N
A/K	0.9942	likely_pathogenic	0.9802	pathogenic	-0.913	Destabilizing	0.833	D	0.739	deleterious	None	None	None	None	N
A/L	0.8144	likely_pathogenic	0.6432	pathogenic	0.245	Stabilizing	0.74	D	0.707	prob.delet.	None	None	None	None	N
A/M	0.7803	likely_pathogenic	0.5808	pathogenic	-0.274	Destabilizing	0.996	D	0.719	prob.delet.	None	None	None	None	N
A/N	0.9306	likely_pathogenic	0.8236	pathogenic	-1.618	Destabilizing	0.833	D	0.757	deleterious	None	None	None	None	N
A/P	0.9975	likely_pathogenic	0.9965	pathogenic	-0.208	Destabilizing	0.938	D	0.747	deleterious	N	0.432051466	None	None	N
A/Q	0.9306	likely_pathogenic	0.8351	pathogenic	-1.18	Destabilizing	0.909	D	0.741	deleterious	None	None	None	None	N
A/R	0.9767	likely_pathogenic	0.9407	pathogenic	-1.414	Destabilizing	0.909	D	0.755	deleterious	None	None	None	None	N
A/S	0.2099	likely_benign	0.1449	benign	-1.82	Destabilizing	0.028	N	0.319	neutral	N	0.421728481	None	None	N
A/T	0.4645	ambiguous	0.2357	benign	-1.39	Destabilizing	0.028	N	0.37	neutral	N	0.437903525	None	None	N
A/V	0.6775	likely_pathogenic	0.4324	ambiguous	-0.208	Destabilizing	0.682	D	0.658	prob.neutral	N	0.42524209	None	None	N
A/W	0.9859	likely_pathogenic	0.9657	pathogenic	-1.193	Destabilizing	0.996	D	0.697	prob.delet.	None	None	None	None	N
A/Y	0.9506	likely_pathogenic	0.8765	pathogenic	-0.819	Destabilizing	0.984	D	0.764	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.