TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24894	74905;74906;74907	chr2:178571452;178571451;178571450	chr2:179436179;179436178;179436177
N2AB	23253	69982;69983;69984	chr2:178571452;178571451;178571450	chr2:179436179;179436178;179436177
N2A	22326	67201;67202;67203	chr2:178571452;178571451;178571450	chr2:179436179;179436178;179436177
N2B	15829	47710;47711;47712	chr2:178571452;178571451;178571450	chr2:179436179;179436178;179436177
Novex-1	15954	48085;48086;48087	chr2:178571452;178571451;178571450	chr2:179436179;179436178;179436177
Novex-2	16021	48286;48287;48288	chr2:178571452;178571451;178571450	chr2:179436179;179436178;179436177
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Fn3-68
• Domain position: 87
• Structural Position: 120
• Q(SASA): 0.3038
• 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/H	None	None	0.954	N	0.515	0.092	0.273503213844	gnomAD-4.0.0	3.18406E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71889E-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
Y/A	0.3092	likely_benign	0.3222	benign	-2.277	Highly Destabilizing	0.345	N	0.449	neutral	None	None	None	None	N
Y/C	0.1212	likely_benign	0.1292	benign	-0.846	Destabilizing	0.007	N	0.468	neutral	N	0.473731734	None	None	N
Y/D	0.504	ambiguous	0.5371	ambiguous	-0.999	Destabilizing	0.662	D	0.6	neutral	N	0.473731734	None	None	N
Y/E	0.8	likely_pathogenic	0.8152	pathogenic	-0.884	Destabilizing	0.561	D	0.558	neutral	None	None	None	None	N
Y/F	0.0729	likely_benign	0.0702	benign	-0.861	Destabilizing	0.001	N	0.196	neutral	N	0.441092667	None	None	N
Y/G	0.3366	likely_benign	0.3488	ambiguous	-2.618	Highly Destabilizing	0.561	D	0.56	neutral	None	None	None	None	N
Y/H	0.2356	likely_benign	0.2554	benign	-0.947	Destabilizing	0.954	D	0.515	neutral	N	0.511974117	None	None	N
Y/I	0.4604	ambiguous	0.4585	ambiguous	-1.224	Destabilizing	0.209	N	0.42	neutral	None	None	None	None	N
Y/K	0.8493	likely_pathogenic	0.8521	pathogenic	-1.089	Destabilizing	0.561	D	0.547	neutral	None	None	None	None	N
Y/L	0.4493	ambiguous	0.4207	ambiguous	-1.224	Destabilizing	0.002	N	0.283	neutral	None	None	None	None	N
Y/M	0.6061	likely_pathogenic	0.5948	pathogenic	-0.842	Destabilizing	0.818	D	0.525	neutral	None	None	None	None	N
Y/N	0.2656	likely_benign	0.2929	benign	-1.485	Destabilizing	0.873	D	0.631	neutral	N	0.473478244	None	None	N
Y/P	0.2939	likely_benign	0.3179	benign	-1.573	Destabilizing	0.002	N	0.544	neutral	None	None	None	None	N
Y/Q	0.6991	likely_pathogenic	0.7136	pathogenic	-1.38	Destabilizing	0.901	D	0.555	neutral	None	None	None	None	N
Y/R	0.7315	likely_pathogenic	0.7347	pathogenic	-0.698	Destabilizing	0.901	D	0.631	neutral	None	None	None	None	N
Y/S	0.1581	likely_benign	0.1745	benign	-2.04	Highly Destabilizing	0.491	N	0.548	neutral	N	0.471703817	None	None	N
Y/T	0.4188	ambiguous	0.4242	ambiguous	-1.825	Destabilizing	0.561	D	0.541	neutral	None	None	None	None	N
Y/V	0.3397	likely_benign	0.3407	ambiguous	-1.573	Destabilizing	0.007	N	0.292	neutral	None	None	None	None	N
Y/W	0.3328	likely_benign	0.327	benign	-0.38	Destabilizing	0.965	D	0.544	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.