TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9470	28633;28634;28635	chr2:178710689;178710688;178710687	chr2:179575416;179575415;179575414
N2AB	9153	27682;27683;27684	chr2:178710689;178710688;178710687	chr2:179575416;179575415;179575414
N2A	8226	24901;24902;24903	chr2:178710689;178710688;178710687	chr2:179575416;179575415;179575414
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: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Ig-80
• Domain position: 74
• Structural Position: 157
• Q(SASA): 0.406
• 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
Y/C	rs781236320	-0.38	0.873	None	0.504	0.374	0.503744809241	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
Y/A	0.2474	likely_benign	0.3607	ambiguous	-1.816	Destabilizing	0.036	N	0.393	neutral	None	None	None	None	N
Y/C	0.1288	likely_benign	0.1485	benign	-0.481	Destabilizing	0.873	D	0.504	neutral	None	None	None	None	N
Y/D	0.1821	likely_benign	0.2396	benign	0.307	Stabilizing	0.061	N	0.447	neutral	None	None	None	None	N
Y/E	0.3896	ambiguous	0.49	ambiguous	0.354	Stabilizing	0.002	N	0.417	neutral	None	None	None	None	N
Y/F	0.086	likely_benign	0.0917	benign	-0.827	Destabilizing	None	N	0.188	neutral	None	None	None	None	N
Y/G	0.2931	likely_benign	0.4604	ambiguous	-2.087	Highly Destabilizing	0.08	N	0.449	neutral	None	None	None	None	N
Y/H	0.0843	likely_benign	0.1144	benign	-0.468	Destabilizing	None	N	0.142	neutral	None	None	None	None	N
Y/I	0.2436	likely_benign	0.3107	benign	-1.038	Destabilizing	0.174	N	0.495	neutral	None	None	None	None	N
Y/K	0.3453	ambiguous	0.5163	ambiguous	-0.435	Destabilizing	0.002	N	0.4	neutral	None	None	None	None	N
Y/L	0.2303	likely_benign	0.3352	benign	-1.038	Destabilizing	0.08	N	0.364	neutral	None	None	None	None	N
Y/M	0.3694	ambiguous	0.4836	ambiguous	-0.663	Destabilizing	0.749	D	0.486	neutral	None	None	None	None	N
Y/N	0.0895	likely_benign	0.1277	benign	-0.565	Destabilizing	0.061	N	0.457	neutral	None	None	None	None	N
Y/P	0.9404	likely_pathogenic	0.9714	pathogenic	-1.286	Destabilizing	0.46	N	0.534	neutral	None	None	None	None	N
Y/Q	0.2216	likely_benign	0.3474	ambiguous	-0.573	Destabilizing	0.007	N	0.242	neutral	None	None	None	None	N
Y/R	0.2048	likely_benign	0.3207	benign	0.031	Stabilizing	0.08	N	0.454	neutral	None	None	None	None	N
Y/S	0.0804	likely_benign	0.111	benign	-1.241	Destabilizing	0.002	N	0.397	neutral	None	None	None	None	N
Y/T	0.157	likely_benign	0.2172	benign	-1.105	Destabilizing	0.08	N	0.453	neutral	None	None	None	None	N
Y/V	0.1953	likely_benign	0.2392	benign	-1.286	Destabilizing	0.148	N	0.403	neutral	None	None	None	None	N
Y/W	0.3577	ambiguous	0.4471	ambiguous	-0.491	Destabilizing	0.901	D	0.507	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.