TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29595	89008;89009;89010	chr2:178554564;178554563;178554562	chr2:179419291;179419290;179419289
N2AB	27954	84085;84086;84087	chr2:178554564;178554563;178554562	chr2:179419291;179419290;179419289
N2A	27027	81304;81305;81306	chr2:178554564;178554563;178554562	chr2:179419291;179419290;179419289
N2B	20530	61813;61814;61815	chr2:178554564;178554563;178554562	chr2:179419291;179419290;179419289
Novex-1	20655	62188;62189;62190	chr2:178554564;178554563;178554562	chr2:179419291;179419290;179419289
Novex-2	20722	62389;62390;62391	chr2:178554564;178554563;178554562	chr2:179419291;179419290;179419289
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Fn3-103
• Domain position: 63
• Structural Position: 93
• Q(SASA): 0.1443
• 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
T/N	rs1575546136	None	0.995	N	0.782	0.325	0.417081434665	gnomAD-4.0.0	1.59107E-06	None	None	None	None	N	None	0	0	None	0	2.77485E-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
T/A	0.0701	likely_benign	0.0753	benign	-0.888	Destabilizing	0.64	D	0.682	prob.neutral	N	0.347051929	None	None	N
T/C	0.3659	ambiguous	0.4107	ambiguous	-0.546	Destabilizing	0.999	D	0.797	deleterious	None	None	None	None	N
T/D	0.8733	likely_pathogenic	0.8827	pathogenic	-0.284	Destabilizing	0.996	D	0.835	deleterious	None	None	None	None	N
T/E	0.7984	likely_pathogenic	0.8033	pathogenic	-0.097	Destabilizing	0.988	D	0.818	deleterious	None	None	None	None	N
T/F	0.5763	likely_pathogenic	0.6212	pathogenic	-0.809	Destabilizing	0.988	D	0.845	deleterious	None	None	None	None	N
T/G	0.4505	ambiguous	0.4823	ambiguous	-1.278	Destabilizing	0.959	D	0.795	deleterious	None	None	None	None	N
T/H	0.6571	likely_pathogenic	0.6776	pathogenic	-1.268	Destabilizing	0.999	D	0.83	deleterious	None	None	None	None	N
T/I	0.2014	likely_benign	0.2315	benign	0.121	Stabilizing	0.64	D	0.754	deleterious	N	0.362805241	None	None	N
T/K	0.7923	likely_pathogenic	0.7796	pathogenic	0.031	Stabilizing	0.988	D	0.819	deleterious	None	None	None	None	N
T/L	0.1697	likely_benign	0.1804	benign	0.121	Stabilizing	0.702	D	0.731	prob.delet.	None	None	None	None	N
T/M	0.1221	likely_benign	0.1315	benign	-0.012	Destabilizing	0.988	D	0.795	deleterious	None	None	None	None	N
T/N	0.3858	ambiguous	0.4151	ambiguous	-0.615	Destabilizing	0.995	D	0.782	deleterious	N	0.490332195	None	None	N
T/P	0.5272	ambiguous	0.5475	ambiguous	-0.184	Destabilizing	0.995	D	0.837	deleterious	N	0.452891315	None	None	N
T/Q	0.6382	likely_pathogenic	0.6474	pathogenic	-0.371	Destabilizing	0.996	D	0.805	deleterious	None	None	None	None	N
T/R	0.7424	likely_pathogenic	0.7276	pathogenic	-0.216	Destabilizing	0.996	D	0.821	deleterious	None	None	None	None	N
T/S	0.1799	likely_benign	0.1989	benign	-1.012	Destabilizing	0.946	D	0.728	prob.delet.	N	0.45237124	None	None	N
T/V	0.1201	likely_benign	0.1337	benign	-0.184	Destabilizing	0.015	N	0.315	neutral	None	None	None	None	N
T/W	0.9254	likely_pathogenic	0.9372	pathogenic	-0.859	Destabilizing	0.999	D	0.828	deleterious	None	None	None	None	N
T/Y	0.6963	likely_pathogenic	0.7221	pathogenic	-0.462	Destabilizing	0.996	D	0.844	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.