TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27474	82645;82646;82647	chr2:178563712;178563711;178563710	chr2:179428439;179428438;179428437
N2AB	25833	77722;77723;77724	chr2:178563712;178563711;178563710	chr2:179428439;179428438;179428437
N2A	24906	74941;74942;74943	chr2:178563712;178563711;178563710	chr2:179428439;179428438;179428437
N2B	18409	55450;55451;55452	chr2:178563712;178563711;178563710	chr2:179428439;179428438;179428437
Novex-1	18534	55825;55826;55827	chr2:178563712;178563711;178563710	chr2:179428439;179428438;179428437
Novex-2	18601	56026;56027;56028	chr2:178563712;178563711;178563710	chr2:179428439;179428438;179428437
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Fn3-88
• Domain position: 6
• Structural Position: 6
• Q(SASA): 0.4115
• 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/L	rs781507920	None	0.97	N	0.739	0.291	0.470237251169	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.88E-06	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	0.0739	likely_benign	0.0756	benign	-0.705	Destabilizing	0.489	N	0.495	neutral	N	0.515614642	None	None	N
S/C	0.1149	likely_benign	0.1124	benign	-0.577	Destabilizing	0.998	D	0.715	prob.delet.	None	None	None	None	N
S/D	0.3409	ambiguous	0.3575	ambiguous	-0.753	Destabilizing	0.86	D	0.597	neutral	None	None	None	None	N
S/E	0.4632	ambiguous	0.4772	ambiguous	-0.716	Destabilizing	0.86	D	0.563	neutral	None	None	None	None	N
S/F	0.2796	likely_benign	0.2605	benign	-0.78	Destabilizing	0.993	D	0.793	deleterious	None	None	None	None	N
S/G	0.0587	likely_benign	0.0592	benign	-0.998	Destabilizing	0.019	N	0.211	neutral	None	None	None	None	N
S/H	0.3995	ambiguous	0.4023	ambiguous	-1.569	Destabilizing	0.998	D	0.718	prob.delet.	None	None	None	None	N
S/I	0.2399	likely_benign	0.2504	benign	-0.023	Destabilizing	0.993	D	0.79	deleterious	None	None	None	None	N
S/K	0.6164	likely_pathogenic	0.6128	pathogenic	-0.822	Destabilizing	0.076	N	0.302	neutral	None	None	None	None	N
S/L	0.1162	likely_benign	0.1142	benign	-0.023	Destabilizing	0.97	D	0.739	prob.delet.	N	0.518385588	None	None	N
S/M	0.2203	likely_benign	0.2156	benign	0.183	Stabilizing	0.998	D	0.709	prob.delet.	None	None	None	None	N
S/N	0.1537	likely_benign	0.1532	benign	-0.933	Destabilizing	0.86	D	0.601	neutral	None	None	None	None	N
S/P	0.3851	ambiguous	0.494	ambiguous	-0.215	Destabilizing	0.99	D	0.756	deleterious	N	0.514961281	None	None	N
S/Q	0.4607	ambiguous	0.4662	ambiguous	-1.004	Destabilizing	0.956	D	0.613	neutral	None	None	None	None	N
S/R	0.5819	likely_pathogenic	0.5744	pathogenic	-0.825	Destabilizing	0.915	D	0.714	prob.delet.	None	None	None	None	N
S/T	0.0896	likely_benign	0.0948	benign	-0.811	Destabilizing	0.904	D	0.567	neutral	N	0.480923278	None	None	N
S/V	0.1903	likely_benign	0.2035	benign	-0.215	Destabilizing	0.978	D	0.736	prob.delet.	None	None	None	None	N
S/W	0.5191	ambiguous	0.4984	ambiguous	-0.838	Destabilizing	0.998	D	0.774	deleterious	None	None	None	None	N
S/Y	0.2752	likely_benign	0.249	benign	-0.536	Destabilizing	0.993	D	0.791	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.