TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35649	107170;107171;107172	chr2:178528806;178528805;178528804	chr2:179393533;179393532;179393531
N2AB	34008	102247;102248;102249	chr2:178528806;178528805;178528804	chr2:179393533;179393532;179393531
N2A	33081	99466;99467;99468	chr2:178528806;178528805;178528804	chr2:179393533;179393532;179393531
N2B	26584	79975;79976;79977	chr2:178528806;178528805;178528804	chr2:179393533;179393532;179393531
Novex-1	26709	80350;80351;80352	chr2:178528806;178528805;178528804	chr2:179393533;179393532;179393531
Novex-2	26776	80551;80552;80553	chr2:178528806;178528805;178528804	chr2:179393533;179393532;179393531
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-167
• Domain position: 43
• Structural Position: 111
• Q(SASA): 0.7478
• 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
E/D	rs764693838	0.051	None	N	0.181	0.065	0.117506650769	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.87E-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
E/A	0.2082	likely_benign	0.1884	benign	-0.186	Destabilizing	0.052	N	0.413	neutral	N	0.453226884	None	None	N
E/C	0.9481	likely_pathogenic	0.9242	pathogenic	-0.054	Destabilizing	0.935	D	0.497	neutral	None	None	None	None	N
E/D	0.1326	likely_benign	0.102	benign	-0.211	Destabilizing	None	N	0.181	neutral	N	0.422210544	None	None	N
E/F	0.8954	likely_pathogenic	0.8422	pathogenic	-0.157	Destabilizing	0.791	D	0.448	neutral	None	None	None	None	N
E/G	0.2038	likely_benign	0.1926	benign	-0.337	Destabilizing	None	N	0.31	neutral	N	0.451319942	None	None	N
E/H	0.6536	likely_pathogenic	0.5727	pathogenic	0.261	Stabilizing	0.555	D	0.384	neutral	None	None	None	None	N
E/I	0.6074	likely_pathogenic	0.5278	ambiguous	0.163	Stabilizing	0.555	D	0.442	neutral	None	None	None	None	N
E/K	0.1469	likely_benign	0.1452	benign	0.43	Stabilizing	0.117	N	0.417	neutral	N	0.453053525	None	None	N
E/L	0.6034	likely_pathogenic	0.529	ambiguous	0.163	Stabilizing	0.38	N	0.433	neutral	None	None	None	None	N
E/M	0.6468	likely_pathogenic	0.5952	pathogenic	0.111	Stabilizing	0.935	D	0.443	neutral	None	None	None	None	N
E/N	0.3182	likely_benign	0.2421	benign	0.166	Stabilizing	0.081	N	0.412	neutral	None	None	None	None	N
E/P	0.4701	ambiguous	0.4071	ambiguous	0.065	Stabilizing	0.555	D	0.387	neutral	None	None	None	None	N
E/Q	0.2291	likely_benign	0.2132	benign	0.192	Stabilizing	0.117	N	0.409	neutral	N	0.453746959	None	None	N
E/R	0.2903	likely_benign	0.2779	benign	0.628	Stabilizing	0.38	N	0.389	neutral	None	None	None	None	N
E/S	0.2482	likely_benign	0.207	benign	0.012	Stabilizing	0.081	N	0.403	neutral	None	None	None	None	N
E/T	0.3384	likely_benign	0.2845	benign	0.14	Stabilizing	0.149	N	0.394	neutral	None	None	None	None	N
E/V	0.3807	ambiguous	0.3308	benign	0.065	Stabilizing	0.484	N	0.392	neutral	N	0.454440392	None	None	N
E/W	0.9345	likely_pathogenic	0.916	pathogenic	-0.063	Destabilizing	0.935	D	0.525	neutral	None	None	None	None	N
E/Y	0.8139	likely_pathogenic	0.74	pathogenic	0.075	Stabilizing	0.791	D	0.431	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.