TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16101	48526;48527;48528	chr2:178616490;178616489;178616488	chr2:179481217;179481216;179481215
N2AB	14460	43603;43604;43605	chr2:178616490;178616489;178616488	chr2:179481217;179481216;179481215
N2A	13533	40822;40823;40824	chr2:178616490;178616489;178616488	chr2:179481217;179481216;179481215
N2B	7036	21331;21332;21333	chr2:178616490;178616489;178616488	chr2:179481217;179481216;179481215
Novex-1	7161	21706;21707;21708	chr2:178616490;178616489;178616488	chr2:179481217;179481216;179481215
Novex-2	7228	21907;21908;21909	chr2:178616490;178616489;178616488	chr2:179481217;179481216;179481215
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: Fn3-4
• Domain position: 47
• Structural Position: 64
• Q(SASA): 0.7219
• 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	0.987	D	0.501	0.362	0.41859458845	gnomAD-4.0.0	1.59478E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.88303E-05	0	0	0	0
T/S	rs1450802850	-0.306	0.989	N	0.445	0.139	0.163833314356	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
T/S	rs1450802850	-0.306	0.989	N	0.445	0.139	0.163833314356	gnomAD-4.0.0	1.59473E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43443E-05	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	0.1081	likely_benign	0.1218	benign	-0.46	Destabilizing	0.977	D	0.441	neutral	N	0.470132343	None	None	N
T/C	0.6148	likely_pathogenic	0.6568	pathogenic	-0.349	Destabilizing	1.0	D	0.561	neutral	None	None	None	None	N
T/D	0.7349	likely_pathogenic	0.7586	pathogenic	0.299	Stabilizing	0.999	D	0.541	neutral	None	None	None	None	N
T/E	0.6374	likely_pathogenic	0.6583	pathogenic	0.246	Stabilizing	0.998	D	0.524	neutral	None	None	None	None	N
T/F	0.465	ambiguous	0.489	ambiguous	-0.82	Destabilizing	0.995	D	0.605	neutral	None	None	None	None	N
T/G	0.2979	likely_benign	0.3222	benign	-0.622	Destabilizing	0.998	D	0.521	neutral	None	None	None	None	N
T/H	0.4876	ambiguous	0.5274	ambiguous	-0.788	Destabilizing	1.0	D	0.612	neutral	None	None	None	None	N
T/I	0.337	likely_benign	0.3689	ambiguous	-0.146	Destabilizing	0.987	D	0.501	neutral	D	0.570140111	None	None	N
T/K	0.4936	ambiguous	0.518	ambiguous	-0.416	Destabilizing	0.993	D	0.516	neutral	N	0.464062798	None	None	N
T/L	0.1867	likely_benign	0.206	benign	-0.146	Destabilizing	0.906	D	0.468	neutral	None	None	None	None	N
T/M	0.1229	likely_benign	0.1356	benign	-0.123	Destabilizing	0.921	D	0.44	neutral	None	None	None	None	N
T/N	0.193	likely_benign	0.2224	benign	-0.214	Destabilizing	0.999	D	0.523	neutral	None	None	None	None	N
T/P	0.3589	ambiguous	0.3784	ambiguous	-0.221	Destabilizing	0.999	D	0.506	neutral	N	0.507090179	None	None	N
T/Q	0.406	ambiguous	0.4246	ambiguous	-0.389	Destabilizing	0.998	D	0.523	neutral	None	None	None	None	N
T/R	0.4367	ambiguous	0.455	ambiguous	-0.134	Destabilizing	0.997	D	0.512	neutral	N	0.477165509	None	None	N
T/S	0.1514	likely_benign	0.1737	benign	-0.468	Destabilizing	0.989	D	0.445	neutral	N	0.472578312	None	None	N
T/V	0.2343	likely_benign	0.26	benign	-0.221	Destabilizing	0.966	D	0.447	neutral	None	None	None	None	N
T/W	0.8338	likely_pathogenic	0.8335	pathogenic	-0.818	Destabilizing	1.0	D	0.653	neutral	None	None	None	None	N
T/Y	0.501	ambiguous	0.5164	ambiguous	-0.549	Destabilizing	0.998	D	0.609	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.