TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28143	84652;84653;84654	chr2:178561705;178561704;178561703	chr2:179426432;179426431;179426430
N2AB	26502	79729;79730;79731	chr2:178561705;178561704;178561703	chr2:179426432;179426431;179426430
N2A	25575	76948;76949;76950	chr2:178561705;178561704;178561703	chr2:179426432;179426431;179426430
N2B	19078	57457;57458;57459	chr2:178561705;178561704;178561703	chr2:179426432;179426431;179426430
Novex-1	19203	57832;57833;57834	chr2:178561705;178561704;178561703	chr2:179426432;179426431;179426430
Novex-2	19270	58033;58034;58035	chr2:178561705;178561704;178561703	chr2:179426432;179426431;179426430
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Fn3-92
• Domain position: 89
• Structural Position: 123
• Q(SASA): 0.2059
• 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
S/F	rs878971321	None	0.981	N	0.789	0.404	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
S/F	rs878971321	None	0.981	N	0.789	0.404	None	gnomAD-4.0.0	6.57039E-06	None	None	None	None	N	None	2.41266E-05	0	None	0	0	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
S/A	0.3945	ambiguous	0.3723	ambiguous	-0.871	Destabilizing	0.595	D	0.473	neutral	N	0.51245412	None	None	N
S/C	0.3907	ambiguous	0.3934	ambiguous	-0.624	Destabilizing	0.998	D	0.674	prob.neutral	N	0.501559679	None	None	N
S/D	0.9412	likely_pathogenic	0.9335	pathogenic	-0.185	Destabilizing	0.904	D	0.595	neutral	None	None	None	None	N
S/E	0.9836	likely_pathogenic	0.9818	pathogenic	-0.112	Destabilizing	0.904	D	0.603	neutral	None	None	None	None	N
S/F	0.9087	likely_pathogenic	0.8981	pathogenic	-0.885	Destabilizing	0.981	D	0.789	deleterious	N	0.486720654	None	None	N
S/G	0.3555	ambiguous	0.3743	ambiguous	-1.182	Destabilizing	0.904	D	0.544	neutral	None	None	None	None	N
S/H	0.9493	likely_pathogenic	0.9461	pathogenic	-1.49	Destabilizing	0.999	D	0.656	prob.neutral	None	None	None	None	N
S/I	0.8208	likely_pathogenic	0.7945	pathogenic	-0.128	Destabilizing	0.971	D	0.738	deleterious	None	None	None	None	N
S/K	0.9958	likely_pathogenic	0.995	pathogenic	-0.37	Destabilizing	0.904	D	0.597	neutral	None	None	None	None	N
S/L	0.628	likely_pathogenic	0.6215	pathogenic	-0.128	Destabilizing	0.825	D	0.677	prob.neutral	None	None	None	None	N
S/M	0.7087	likely_pathogenic	0.6774	pathogenic	-0.083	Destabilizing	0.999	D	0.651	prob.neutral	None	None	None	None	N
S/N	0.7923	likely_pathogenic	0.7881	pathogenic	-0.557	Destabilizing	0.904	D	0.606	neutral	None	None	None	None	N
S/P	0.9748	likely_pathogenic	0.9772	pathogenic	-0.341	Destabilizing	0.981	D	0.653	prob.neutral	N	0.455771331	None	None	N
S/Q	0.9778	likely_pathogenic	0.9749	pathogenic	-0.58	Destabilizing	0.985	D	0.616	neutral	None	None	None	None	N
S/R	0.9949	likely_pathogenic	0.995	pathogenic	-0.444	Destabilizing	0.971	D	0.645	neutral	None	None	None	None	N
S/T	0.1428	likely_benign	0.1397	benign	-0.55	Destabilizing	0.087	N	0.356	neutral	N	0.505373432	None	None	N
S/V	0.7732	likely_pathogenic	0.746	pathogenic	-0.341	Destabilizing	0.943	D	0.7	prob.delet.	None	None	None	None	N
S/W	0.9481	likely_pathogenic	0.9467	pathogenic	-0.856	Destabilizing	0.999	D	0.825	deleterious	None	None	None	None	N
S/Y	0.882	likely_pathogenic	0.8785	pathogenic	-0.541	Destabilizing	0.994	D	0.794	deleterious	N	0.518396487	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.