TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20163	60712;60713;60714	chr2:178591238;178591237;178591236	chr2:179455965;179455964;179455963
N2AB	18522	55789;55790;55791	chr2:178591238;178591237;178591236	chr2:179455965;179455964;179455963
N2A	17595	53008;53009;53010	chr2:178591238;178591237;178591236	chr2:179455965;179455964;179455963
N2B	11098	33517;33518;33519	chr2:178591238;178591237;178591236	chr2:179455965;179455964;179455963
Novex-1	11223	33892;33893;33894	chr2:178591238;178591237;178591236	chr2:179455965;179455964;179455963
Novex-2	11290	34093;34094;34095	chr2:178591238;178591237;178591236	chr2:179455965;179455964;179455963
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Ig-120
• Domain position: 84
• Structural Position: 171
• Q(SASA): 0.2577
• 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/V	None	None	0.22	N	0.57	0.239	0.57179433898	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.93751E-06	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
A/C	0.5066	ambiguous	0.5337	ambiguous	-0.969	Destabilizing	0.968	D	0.606	neutral	None	None	None	None	N
A/D	0.3386	likely_benign	0.4358	ambiguous	-1.093	Destabilizing	0.497	N	0.78	deleterious	N	0.490383415	None	None	N
A/E	0.369	ambiguous	0.4625	ambiguous	-1.136	Destabilizing	0.567	D	0.711	prob.delet.	None	None	None	None	N
A/F	0.39	ambiguous	0.4469	ambiguous	-0.848	Destabilizing	0.89	D	0.822	deleterious	None	None	None	None	N
A/G	0.1373	likely_benign	0.1517	benign	-0.962	Destabilizing	0.001	N	0.315	neutral	D	0.524920063	None	None	N
A/H	0.4987	ambiguous	0.5701	pathogenic	-1.084	Destabilizing	0.968	D	0.805	deleterious	None	None	None	None	N
A/I	0.253	likely_benign	0.306	benign	-0.26	Destabilizing	0.726	D	0.742	deleterious	None	None	None	None	N
A/K	0.4622	ambiguous	0.5557	ambiguous	-1.259	Destabilizing	0.567	D	0.709	prob.delet.	None	None	None	None	N
A/L	0.1792	likely_benign	0.2038	benign	-0.26	Destabilizing	0.272	N	0.689	prob.neutral	None	None	None	None	N
A/M	0.2289	likely_benign	0.2443	benign	-0.359	Destabilizing	0.968	D	0.723	prob.delet.	None	None	None	None	N
A/N	0.2526	likely_benign	0.3009	benign	-0.986	Destabilizing	0.567	D	0.822	deleterious	None	None	None	None	N
A/P	0.123	likely_benign	0.1689	benign	-0.375	Destabilizing	0.001	N	0.372	neutral	N	0.499042971	None	None	N
A/Q	0.392	ambiguous	0.4564	ambiguous	-1.142	Destabilizing	0.726	D	0.741	deleterious	None	None	None	None	N
A/R	0.4504	ambiguous	0.5266	ambiguous	-0.863	Destabilizing	0.726	D	0.741	deleterious	None	None	None	None	N
A/S	0.1008	likely_benign	0.1064	benign	-1.281	Destabilizing	0.011	N	0.371	neutral	N	0.414114788	None	None	N
A/T	0.0969	likely_benign	0.104	benign	-1.226	Destabilizing	0.124	N	0.576	neutral	N	0.45530805	None	None	N
A/V	0.141	likely_benign	0.1606	benign	-0.375	Destabilizing	0.22	N	0.57	neutral	N	0.461794092	None	None	N
A/W	0.7669	likely_pathogenic	0.8057	pathogenic	-1.162	Destabilizing	0.968	D	0.792	deleterious	None	None	None	None	N
A/Y	0.543	ambiguous	0.603	pathogenic	-0.771	Destabilizing	0.89	D	0.823	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.