TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28044	84355;84356;84357	chr2:178562002;178562001;178562000	chr2:179426729;179426728;179426727
N2AB	26403	79432;79433;79434	chr2:178562002;178562001;178562000	chr2:179426729;179426728;179426727
N2A	25476	76651;76652;76653	chr2:178562002;178562001;178562000	chr2:179426729;179426728;179426727
N2B	18979	57160;57161;57162	chr2:178562002;178562001;178562000	chr2:179426729;179426728;179426727
Novex-1	19104	57535;57536;57537	chr2:178562002;178562001;178562000	chr2:179426729;179426728;179426727
Novex-2	19171	57736;57737;57738	chr2:178562002;178562001;178562000	chr2:179426729;179426728;179426727
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Ig-142
• Domain position: 82
• Structural Position: 166
• Q(SASA): 0.2582
• 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
I/L	rs369062122	-0.45	None	N	0.116	0.097	0.214338557667	gnomAD-2.1.1	3.18E-05	None	None	None	None	N	None	1.14732E-04	0	None	0	0	None	0	None	0	0	0
I/L	rs369062122	-0.45	None	N	0.116	0.097	0.214338557667	gnomAD-3.1.2	3.29E-05	None	None	None	None	N	None	1.20616E-04	0	0	0	0	None	0	0	0	0	0
I/L	rs369062122	-0.45	None	N	0.116	0.097	0.214338557667	1000 genomes	1.99681E-04	None	None	None	None	N	None	8E-04	0	None	None	0	0	None	None	None	0	None
I/L	rs369062122	-0.45	None	N	0.116	0.097	0.214338557667	gnomAD-4.0.0	6.81736E-06	None	None	None	None	N	None	7.99637E-05	0	None	0	8.93895E-05	None	0	0	0	0	1.60092E-05
I/M	None	None	0.001	N	0.285	0.048	0.390060412749	gnomAD-4.0.0	1.59208E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43324E-05	0
I/T	rs1004500080	-1.05	None	N	0.183	0.086	0.33340067248	gnomAD-2.1.1	7.16E-06	None	None	None	None	N	None	8.27E-05	0	None	0	0	None	0	None	0	0	0
I/T	rs1004500080	-1.05	None	N	0.183	0.086	0.33340067248	gnomAD-3.1.2	2.63E-05	None	None	None	None	N	None	9.65E-05	0	0	0	0	None	0	0	0	0	0
I/T	rs1004500080	-1.05	None	N	0.183	0.086	0.33340067248	gnomAD-4.0.0	5.57836E-06	None	None	None	None	N	None	8.0094E-05	0	None	0	0	None	0	0	2.54302E-06	0	0
I/V	rs369062122	-0.666	None	N	0.121	0.074	None	gnomAD-2.1.1	2.51E-05	None	None	None	None	N	None	1.24059E-04	0	None	0	0	None	6.54E-05	None	8.02E-05	0	0
I/V	rs369062122	-0.666	None	N	0.121	0.074	None	gnomAD-3.1.2	3.94E-05	None	None	None	None	N	None	1.44739E-04	0	0	0	0	None	0	0	0	0	0
I/V	rs369062122	-0.666	None	N	0.121	0.074	None	gnomAD-4.0.0	8.05747E-06	None	None	None	None	N	None	1.06792E-04	0	None	0	0	None	3.12598E-05	0	0	3.29424E-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
I/A	0.1267	likely_benign	0.154	benign	-1.285	Destabilizing	0.004	N	0.28	neutral	None	None	None	None	N
I/C	0.4517	ambiguous	0.4868	ambiguous	-0.918	Destabilizing	0.245	N	0.537	neutral	None	None	None	None	N
I/D	0.3263	likely_benign	0.3982	ambiguous	-0.429	Destabilizing	0.044	N	0.571	neutral	None	None	None	None	N
I/E	0.2596	likely_benign	0.303	benign	-0.458	Destabilizing	0.018	N	0.487	neutral	None	None	None	None	N
I/F	0.1484	likely_benign	0.1676	benign	-0.963	Destabilizing	0.022	N	0.453	neutral	None	None	None	None	N
I/G	0.3884	ambiguous	0.4756	ambiguous	-1.562	Destabilizing	0.018	N	0.487	neutral	None	None	None	None	N
I/H	0.3245	likely_benign	0.3713	ambiguous	-0.807	Destabilizing	0.497	N	0.593	neutral	None	None	None	None	N
I/K	0.1962	likely_benign	0.2274	benign	-0.766	Destabilizing	None	N	0.351	neutral	N	0.404591228	None	None	N
I/L	0.0963	likely_benign	0.0899	benign	-0.63	Destabilizing	None	N	0.116	neutral	N	0.493269005	None	None	N
I/M	0.082	likely_benign	0.0818	benign	-0.551	Destabilizing	0.001	N	0.285	neutral	N	0.512817558	None	None	N
I/N	0.1328	likely_benign	0.1579	benign	-0.555	Destabilizing	0.044	N	0.613	neutral	None	None	None	None	N
I/P	0.8481	likely_pathogenic	0.8918	pathogenic	-0.815	Destabilizing	0.085	N	0.616	neutral	None	None	None	None	N
I/Q	0.2379	likely_benign	0.2672	benign	-0.742	Destabilizing	0.044	N	0.614	neutral	None	None	None	None	N
I/R	0.1728	likely_benign	0.2075	benign	-0.234	Destabilizing	0.017	N	0.551	neutral	N	0.447131284	None	None	N
I/S	0.1316	likely_benign	0.1636	benign	-1.182	Destabilizing	0.009	N	0.42	neutral	None	None	None	None	N
I/T	0.0848	likely_benign	0.1042	benign	-1.092	Destabilizing	None	N	0.183	neutral	N	0.423870422	None	None	N
I/V	0.0585	likely_benign	0.0626	benign	-0.815	Destabilizing	None	N	0.121	neutral	N	0.43381527	None	None	N
I/W	0.7858	likely_pathogenic	0.8059	pathogenic	-0.98	Destabilizing	0.788	D	0.595	neutral	None	None	None	None	N
I/Y	0.4177	ambiguous	0.429	ambiguous	-0.742	Destabilizing	0.085	N	0.599	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.