TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9086	27481;27482;27483	chr2:178712769;178712768;178712767	chr2:179577496;179577495;179577494
N2AB	8769	26530;26531;26532	chr2:178712769;178712768;178712767	chr2:179577496;179577495;179577494
N2A	7842	23749;23750;23751	chr2:178712769;178712768;178712767	chr2:179577496;179577495;179577494
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Ig-76
• Domain position: 68
• Structural Position: 151
• Q(SASA): 0.26
• 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/C	None	None	0.99	D	0.507	0.495	0.453867917445	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
S/R	None	None	0.81	N	0.537	0.338	0.286465849087	gnomAD-4.0.0	6.84219E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99476E-07	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	0.0914	likely_benign	0.0875	benign	-0.822	Destabilizing	0.009	N	0.138	neutral	None	None	None	None	N
S/C	0.2065	likely_benign	0.1997	benign	-0.433	Destabilizing	0.99	D	0.507	neutral	D	0.543594081	None	None	N
S/D	0.3913	ambiguous	0.4191	ambiguous	0.526	Stabilizing	0.617	D	0.451	neutral	None	None	None	None	N
S/E	0.4854	ambiguous	0.5293	ambiguous	0.501	Stabilizing	0.617	D	0.465	neutral	None	None	None	None	N
S/F	0.4437	ambiguous	0.4305	ambiguous	-1.158	Destabilizing	0.92	D	0.589	neutral	None	None	None	None	N
S/G	0.0741	likely_benign	0.0764	benign	-1.024	Destabilizing	0.334	N	0.494	neutral	N	0.502826441	None	None	N
S/H	0.4417	ambiguous	0.4543	ambiguous	-1.416	Destabilizing	0.992	D	0.509	neutral	None	None	None	None	N
S/I	0.2751	likely_benign	0.2951	benign	-0.396	Destabilizing	0.81	D	0.57	neutral	D	0.522514085	None	None	N
S/K	0.6047	likely_pathogenic	0.658	pathogenic	-0.382	Destabilizing	0.617	D	0.459	neutral	None	None	None	None	N
S/L	0.1853	likely_benign	0.1804	benign	-0.396	Destabilizing	0.447	N	0.524	neutral	None	None	None	None	N
S/M	0.2892	likely_benign	0.2713	benign	-0.125	Destabilizing	0.977	D	0.511	neutral	None	None	None	None	N
S/N	0.1558	likely_benign	0.1597	benign	-0.241	Destabilizing	0.549	D	0.472	neutral	N	0.515575098	None	None	N
S/P	0.6622	likely_pathogenic	0.5947	pathogenic	-0.507	Destabilizing	0.005	N	0.299	neutral	None	None	None	None	N
S/Q	0.4728	ambiguous	0.5046	ambiguous	-0.397	Destabilizing	0.92	D	0.47	neutral	None	None	None	None	N
S/R	0.4996	ambiguous	0.5516	ambiguous	-0.311	Destabilizing	0.81	D	0.537	neutral	N	0.501091694	None	None	N
S/T	0.1157	likely_benign	0.1073	benign	-0.412	Destabilizing	0.004	N	0.327	neutral	N	0.487417984	None	None	N
S/V	0.3347	likely_benign	0.3292	benign	-0.507	Destabilizing	0.447	N	0.53	neutral	None	None	None	None	N
S/W	0.4898	ambiguous	0.511	ambiguous	-1.064	Destabilizing	0.992	D	0.645	neutral	None	None	None	None	N
S/Y	0.3276	likely_benign	0.3357	benign	-0.811	Destabilizing	0.972	D	0.591	neutral	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.