TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30826	92701;92702;92703	chr2:178549150;178549149;178549148	chr2:179413877;179413876;179413875
N2AB	29185	87778;87779;87780	chr2:178549150;178549149;178549148	chr2:179413877;179413876;179413875
N2A	28258	84997;84998;84999	chr2:178549150;178549149;178549148	chr2:179413877;179413876;179413875
N2B	21761	65506;65507;65508	chr2:178549150;178549149;178549148	chr2:179413877;179413876;179413875
Novex-1	21886	65881;65882;65883	chr2:178549150;178549149;178549148	chr2:179413877;179413876;179413875
Novex-2	21953	66082;66083;66084	chr2:178549150;178549149;178549148	chr2:179413877;179413876;179413875
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-113
• Domain position: 6
• Structural Position: 6
• Q(SASA): 0.3113
• 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
T/I	None	None	0.317	N	0.586	0.109	0.247322355667	gnomAD-4.0.0	3.18242E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71592E-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
T/A	0.0536	likely_benign	0.0574	benign	-0.591	Destabilizing	None	N	0.214	neutral	N	0.423128555	None	None	N
T/C	0.2669	likely_benign	0.2957	benign	-0.304	Destabilizing	0.824	D	0.526	neutral	None	None	None	None	N
T/D	0.4058	ambiguous	0.3904	ambiguous	-0.204	Destabilizing	0.081	N	0.559	neutral	None	None	None	None	N
T/E	0.3691	ambiguous	0.3387	benign	-0.219	Destabilizing	0.081	N	0.561	neutral	None	None	None	None	N
T/F	0.2162	likely_benign	0.2425	benign	-0.688	Destabilizing	0.555	D	0.634	neutral	None	None	None	None	N
T/G	0.1162	likely_benign	0.1263	benign	-0.837	Destabilizing	0.001	N	0.391	neutral	None	None	None	None	N
T/H	0.2923	likely_benign	0.3027	benign	-1.181	Destabilizing	0.824	D	0.614	neutral	None	None	None	None	N
T/I	0.1337	likely_benign	0.1472	benign	-0.032	Destabilizing	0.317	N	0.586	neutral	N	0.494644724	None	None	N
T/K	0.31	likely_benign	0.2784	benign	-0.739	Destabilizing	0.062	N	0.553	neutral	N	0.484561016	None	None	N
T/L	0.0818	likely_benign	0.0858	benign	-0.032	Destabilizing	0.081	N	0.52	neutral	None	None	None	None	N
T/M	0.0806	likely_benign	0.084	benign	0.204	Stabilizing	0.935	D	0.531	neutral	None	None	None	None	N
T/N	0.1078	likely_benign	0.1137	benign	-0.585	Destabilizing	0.001	N	0.305	neutral	None	None	None	None	N
T/P	0.1695	likely_benign	0.1796	benign	-0.185	Destabilizing	0.317	N	0.575	neutral	N	0.521425893	None	None	N
T/Q	0.2671	likely_benign	0.2638	benign	-0.733	Destabilizing	0.38	N	0.579	neutral	None	None	None	None	N
T/R	0.2624	likely_benign	0.2412	benign	-0.52	Destabilizing	0.317	N	0.575	neutral	N	0.474805382	None	None	N
T/S	0.0766	likely_benign	0.0797	benign	-0.796	Destabilizing	None	N	0.177	neutral	N	0.422645766	None	None	N
T/V	0.0928	likely_benign	0.0991	benign	-0.185	Destabilizing	0.081	N	0.457	neutral	None	None	None	None	N
T/W	0.5873	likely_pathogenic	0.61	pathogenic	-0.682	Destabilizing	0.935	D	0.687	prob.neutral	None	None	None	None	N
T/Y	0.2639	likely_benign	0.2788	benign	-0.448	Destabilizing	0.555	D	0.636	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.