TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32078	96457;96458;96459	chr2:178543912;178543911;178543910	chr2:179408639;179408638;179408637
N2AB	30437	91534;91535;91536	chr2:178543912;178543911;178543910	chr2:179408639;179408638;179408637
N2A	29510	88753;88754;88755	chr2:178543912;178543911;178543910	chr2:179408639;179408638;179408637
N2B	23013	69262;69263;69264	chr2:178543912;178543911;178543910	chr2:179408639;179408638;179408637
Novex-1	23138	69637;69638;69639	chr2:178543912;178543911;178543910	chr2:179408639;179408638;179408637
Novex-2	23205	69838;69839;69840	chr2:178543912;178543911;178543910	chr2:179408639;179408638;179408637
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: Ig-153
• Domain position: 62
• Structural Position: 148
• Q(SASA): 0.4702
• 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
Y/C	rs1157695554	0.491	1.0	N	0.683	0.577	0.462287137294	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	5.57E-05	None	0	None	0	0	0
Y/C	rs1157695554	0.491	1.0	N	0.683	0.577	0.462287137294	gnomAD-4.0.0	1.59147E-05	None	None	None	None	I	None	0	0	None	0	2.773E-04	None	0	0	0	0	0
Y/S	rs1157695554	-0.149	1.0	N	0.663	0.505	0.520535218364	gnomAD-2.1.1	3.18E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	6.48E-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
Y/A	0.5574	ambiguous	0.5633	ambiguous	-0.501	Destabilizing	1.0	D	0.594	neutral	None	None	None	None	I
Y/C	0.2365	likely_benign	0.2355	benign	0.207	Stabilizing	1.0	D	0.683	prob.neutral	N	0.473845595	None	None	I
Y/D	0.2694	likely_benign	0.2604	benign	0.871	Stabilizing	1.0	D	0.69	prob.neutral	N	0.407201019	None	None	I
Y/E	0.6207	likely_pathogenic	0.6149	pathogenic	0.847	Stabilizing	1.0	D	0.655	neutral	None	None	None	None	I
Y/F	0.1291	likely_benign	0.1306	benign	-0.288	Destabilizing	0.999	D	0.549	neutral	N	0.435217126	None	None	I
Y/G	0.4764	ambiguous	0.4728	ambiguous	-0.676	Destabilizing	1.0	D	0.67	neutral	None	None	None	None	I
Y/H	0.196	likely_benign	0.1938	benign	0.249	Stabilizing	1.0	D	0.672	neutral	N	0.456957835	None	None	I
Y/I	0.6584	likely_pathogenic	0.665	pathogenic	-0.072	Destabilizing	1.0	D	0.671	neutral	None	None	None	None	I
Y/K	0.6072	likely_pathogenic	0.6008	pathogenic	0.288	Stabilizing	1.0	D	0.652	neutral	None	None	None	None	I
Y/L	0.5537	ambiguous	0.5599	ambiguous	-0.072	Destabilizing	0.999	D	0.645	neutral	None	None	None	None	I
Y/M	0.6332	likely_pathogenic	0.6425	pathogenic	0.005	Stabilizing	1.0	D	0.662	neutral	None	None	None	None	I
Y/N	0.1187	likely_benign	0.1177	benign	0.098	Stabilizing	1.0	D	0.677	prob.neutral	N	0.415975218	None	None	I
Y/P	0.953	likely_pathogenic	0.9447	pathogenic	-0.196	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	I
Y/Q	0.5	ambiguous	0.5049	ambiguous	0.156	Stabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	I
Y/R	0.4249	ambiguous	0.4299	ambiguous	0.478	Stabilizing	1.0	D	0.682	prob.neutral	None	None	None	None	I
Y/S	0.2425	likely_benign	0.2437	benign	-0.28	Destabilizing	1.0	D	0.663	neutral	N	0.415337712	None	None	I
Y/T	0.4473	ambiguous	0.4605	ambiguous	-0.212	Destabilizing	1.0	D	0.656	neutral	None	None	None	None	I
Y/V	0.5406	ambiguous	0.5515	ambiguous	-0.196	Destabilizing	1.0	D	0.639	neutral	None	None	None	None	I
Y/W	0.4779	ambiguous	0.4615	ambiguous	-0.484	Destabilizing	1.0	D	0.67	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.