TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3966	12121;12122;12123	chr2:178741337;178741336;178741335	chr2:179606064;179606063;179606062
N2AB	3649	11170;11171;11172	chr2:178741337;178741336;178741335	chr2:179606064;179606063;179606062
N2A	None	None	chr2:None	chr2:None
N2B	3603	11032;11033;11034	chr2:178741337;178741336;178741335	chr2:179606064;179606063;179606062
Novex-1	3728	11407;11408;11409	chr2:178741337;178741336;178741335	chr2:179606064;179606063;179606062
Novex-2	3795	11608;11609;11610	chr2:178741337;178741336;178741335	chr2:179606064;179606063;179606062
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-28
• Domain position: 29
• Structural Position: 43
• Q(SASA): 0.5556
• Predicted PPI site: I

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/D	None	None	0.055	N	0.499	0.053	None	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.66327E-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
A/C	0.4062	ambiguous	0.4149	ambiguous	-0.687	Destabilizing	0.001	N	0.153	neutral	None	None	None	None	I
A/D	0.1914	likely_benign	0.195	benign	-0.573	Destabilizing	0.055	N	0.499	neutral	N	0.507544067	None	None	I
A/E	0.1541	likely_benign	0.1662	benign	-0.733	Destabilizing	0.038	N	0.411	neutral	None	None	None	None	I
A/F	0.2091	likely_benign	0.2084	benign	-0.954	Destabilizing	None	N	0.317	neutral	None	None	None	None	I
A/G	0.1569	likely_benign	0.1613	benign	-0.36	Destabilizing	None	N	0.092	neutral	D	0.616710905	None	None	I
A/H	0.3402	ambiguous	0.3568	ambiguous	-0.445	Destabilizing	0.628	D	0.505	neutral	None	None	None	None	I
A/I	0.1318	likely_benign	0.1456	benign	-0.368	Destabilizing	None	N	0.168	neutral	None	None	None	None	I
A/K	0.2316	likely_benign	0.2572	benign	-0.686	Destabilizing	None	N	0.215	neutral	None	None	None	None	I
A/L	0.1061	likely_benign	0.1192	benign	-0.368	Destabilizing	0.002	N	0.301	neutral	None	None	None	None	I
A/M	0.1465	likely_benign	0.1601	benign	-0.352	Destabilizing	0.214	N	0.435	neutral	None	None	None	None	I
A/N	0.1814	likely_benign	0.1964	benign	-0.301	Destabilizing	0.072	N	0.525	neutral	None	None	None	None	I
A/P	0.1147	likely_benign	0.1251	benign	-0.315	Destabilizing	None	N	0.216	neutral	N	0.472289055	None	None	I
A/Q	0.2123	likely_benign	0.2408	benign	-0.605	Destabilizing	0.214	N	0.461	neutral	None	None	None	None	I
A/R	0.2193	likely_benign	0.2353	benign	-0.199	Destabilizing	0.038	N	0.471	neutral	None	None	None	None	I
A/S	0.0874	likely_benign	0.0917	benign	-0.481	Destabilizing	0.012	N	0.229	neutral	N	0.508860585	None	None	I
A/T	0.0707	likely_benign	0.074	benign	-0.566	Destabilizing	None	N	0.093	neutral	N	0.483018176	None	None	I
A/V	0.0859	likely_benign	0.0898	benign	-0.315	Destabilizing	None	N	0.082	neutral	N	0.49887892	None	None	I
A/W	0.6262	likely_pathogenic	0.6212	pathogenic	-1.098	Destabilizing	0.864	D	0.504	neutral	None	None	None	None	I
A/Y	0.3319	likely_benign	0.3294	benign	-0.75	Destabilizing	0.12	N	0.519	neutral	None	None	None	None	I

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.