TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19988	60187;60188;60189	chr2:178591857;178591856;178591855	chr2:179456584;179456583;179456582
N2AB	18347	55264;55265;55266	chr2:178591857;178591856;178591855	chr2:179456584;179456583;179456582
N2A	17420	52483;52484;52485	chr2:178591857;178591856;178591855	chr2:179456584;179456583;179456582
N2B	10923	32992;32993;32994	chr2:178591857;178591856;178591855	chr2:179456584;179456583;179456582
Novex-1	11048	33367;33368;33369	chr2:178591857;178591856;178591855	chr2:179456584;179456583;179456582
Novex-2	11115	33568;33569;33570	chr2:178591857;178591856;178591855	chr2:179456584;179456583;179456582
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-33
• Domain position: 12
• Structural Position: 14
• Q(SASA): 0.5055
• 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
D/V	None	None	1.0	N	0.711	0.546	0.461759001683	gnomAD-4.0.0	3.18477E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.88267E-05	0	0	0	3.02627E-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
D/A	0.5088	ambiguous	0.4075	ambiguous	-0.431	Destabilizing	1.0	D	0.691	prob.neutral	N	0.518614875	None	None	N
D/C	0.933	likely_pathogenic	0.9257	pathogenic	-0.224	Destabilizing	1.0	D	0.619	neutral	None	None	None	None	N
D/E	0.5652	likely_pathogenic	0.4624	ambiguous	-0.497	Destabilizing	1.0	D	0.381	neutral	N	0.447541423	None	None	N
D/F	0.8838	likely_pathogenic	0.8636	pathogenic	-0.196	Destabilizing	1.0	D	0.637	neutral	None	None	None	None	N
D/G	0.5977	likely_pathogenic	0.4991	ambiguous	-0.709	Destabilizing	1.0	D	0.709	prob.delet.	N	0.4725341	None	None	N
D/H	0.7514	likely_pathogenic	0.7069	pathogenic	-0.381	Destabilizing	1.0	D	0.606	neutral	N	0.489210004	None	None	N
D/I	0.8192	likely_pathogenic	0.7719	pathogenic	0.279	Stabilizing	1.0	D	0.675	neutral	None	None	None	None	N
D/K	0.8854	likely_pathogenic	0.8542	pathogenic	-0.385	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
D/L	0.7788	likely_pathogenic	0.729	pathogenic	0.279	Stabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
D/M	0.9087	likely_pathogenic	0.88	pathogenic	0.52	Stabilizing	1.0	D	0.621	neutral	None	None	None	None	N
D/N	0.3322	likely_benign	0.2582	benign	-0.604	Destabilizing	1.0	D	0.63	neutral	N	0.500490474	None	None	N
D/P	0.9912	likely_pathogenic	0.9902	pathogenic	0.067	Stabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	N
D/Q	0.8103	likely_pathogenic	0.7628	pathogenic	-0.508	Destabilizing	1.0	D	0.678	prob.neutral	None	None	None	None	N
D/R	0.8498	likely_pathogenic	0.8215	pathogenic	-0.165	Destabilizing	1.0	D	0.663	neutral	None	None	None	None	N
D/S	0.4291	ambiguous	0.3369	benign	-0.798	Destabilizing	1.0	D	0.663	neutral	None	None	None	None	N
D/T	0.6662	likely_pathogenic	0.579	pathogenic	-0.588	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
D/V	0.6406	likely_pathogenic	0.5601	ambiguous	0.067	Stabilizing	1.0	D	0.711	prob.delet.	N	0.483827953	None	None	N
D/W	0.97	likely_pathogenic	0.9705	pathogenic	-0.071	Destabilizing	1.0	D	0.625	neutral	None	None	None	None	N
D/Y	0.6246	likely_pathogenic	0.6063	pathogenic	None	Stabilizing	1.0	D	0.617	neutral	N	0.48344956	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.