TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27923	83992;83993;83994	chr2:178562365;178562364;178562363	chr2:179427092;179427091;179427090
N2AB	26282	79069;79070;79071	chr2:178562365;178562364;178562363	chr2:179427092;179427091;179427090
N2A	25355	76288;76289;76290	chr2:178562365;178562364;178562363	chr2:179427092;179427091;179427090
N2B	18858	56797;56798;56799	chr2:178562365;178562364;178562363	chr2:179427092;179427091;179427090
Novex-1	18983	57172;57173;57174	chr2:178562365;178562364;178562363	chr2:179427092;179427091;179427090
Novex-2	19050	57373;57374;57375	chr2:178562365;178562364;178562363	chr2:179427092;179427091;179427090
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: Fn3-91
• Domain position: 61
• Structural Position: 93
• Q(SASA): 0.1366
• 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	rs778728899	-0.743	0.011	N	0.528	0.071	0.136095386433	gnomAD-2.1.1	4.09E-06	None	None	None	None	N	None	0	0	None	0	5.62E-05	None	0	None	0	0	0
I/L	rs778728899	-0.743	0.011	N	0.528	0.071	0.136095386433	gnomAD-4.0.0	6.85695E-07	None	None	None	None	N	None	0	0	None	0	2.52283E-05	None	0	0	0	0	0
I/M	rs1704000371	None	0.632	N	0.673	0.315	0.513226221338	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	0	4.77555E-04
I/M	rs1704000371	None	0.632	N	0.673	0.315	0.513226221338	gnomAD-4.0.0	6.57082E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	4.77555E-04
I/T	rs757118021	-1.917	0.004	N	0.524	0.358	None	gnomAD-2.1.1	1.09E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	2.37E-05	0
I/T	rs757118021	-1.917	0.004	N	0.524	0.358	None	gnomAD-3.1.2	3.29E-05	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	5.88E-05	0	0
I/T	rs757118021	-1.917	0.004	N	0.524	0.358	None	gnomAD-4.0.0	1.28596E-05	None	None	None	None	N	None	1.69503E-05	0	None	0	0	None	0	0	1.91923E-05	1.35322E-05	0
I/V	rs778728899	-1.132	None	N	0.213	0.132	0.159798565429	gnomAD-2.1.1	4.09E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.99E-06	0
I/V	rs778728899	-1.132	None	N	0.213	0.132	0.159798565429	gnomAD-4.0.0	1.37139E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.80084E-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
I/A	0.7776	likely_pathogenic	0.8216	pathogenic	-2.453	Highly Destabilizing	0.529	D	0.725	prob.delet.	None	None	None	None	N
I/C	0.852	likely_pathogenic	0.8992	pathogenic	-1.964	Destabilizing	0.993	D	0.75	deleterious	None	None	None	None	N
I/D	0.9939	likely_pathogenic	0.9953	pathogenic	-1.81	Destabilizing	0.95	D	0.835	deleterious	None	None	None	None	N
I/E	0.9867	likely_pathogenic	0.9889	pathogenic	-1.662	Destabilizing	0.934	D	0.825	deleterious	None	None	None	None	N
I/F	0.4114	ambiguous	0.4556	ambiguous	-1.653	Destabilizing	0.883	D	0.722	prob.delet.	None	None	None	None	N
I/G	0.9725	likely_pathogenic	0.98	pathogenic	-2.942	Highly Destabilizing	0.95	D	0.816	deleterious	None	None	None	None	N
I/H	0.9658	likely_pathogenic	0.9745	pathogenic	-2.166	Highly Destabilizing	0.995	D	0.831	deleterious	None	None	None	None	N
I/K	0.9723	likely_pathogenic	0.9765	pathogenic	-1.74	Destabilizing	0.297	N	0.833	deleterious	N	0.499885201	None	None	N
I/L	0.1831	likely_benign	0.2208	benign	-1.084	Destabilizing	0.011	N	0.528	neutral	N	0.438033719	None	None	N
I/M	0.2879	likely_benign	0.3374	benign	-1.024	Destabilizing	0.632	D	0.673	neutral	N	0.485388571	None	None	N
I/N	0.9421	likely_pathogenic	0.9548	pathogenic	-1.834	Destabilizing	0.95	D	0.837	deleterious	None	None	None	None	N
I/P	0.9822	likely_pathogenic	0.9824	pathogenic	-1.516	Destabilizing	0.975	D	0.835	deleterious	None	None	None	None	N
I/Q	0.9719	likely_pathogenic	0.9771	pathogenic	-1.802	Destabilizing	0.941	D	0.826	deleterious	None	None	None	None	N
I/R	0.9544	likely_pathogenic	0.9615	pathogenic	-1.346	Destabilizing	0.851	D	0.837	deleterious	N	0.506468567	None	None	N
I/S	0.9081	likely_pathogenic	0.9274	pathogenic	-2.67	Highly Destabilizing	0.731	D	0.79	deleterious	None	None	None	None	N
I/T	0.8444	likely_pathogenic	0.8699	pathogenic	-2.363	Highly Destabilizing	0.004	N	0.524	neutral	N	0.48564206	None	None	N
I/V	0.0627	likely_benign	0.0669	benign	-1.516	Destabilizing	None	N	0.213	neutral	N	0.381084358	None	None	N
I/W	0.976	likely_pathogenic	0.9834	pathogenic	-1.788	Destabilizing	0.998	D	0.819	deleterious	None	None	None	None	N
I/Y	0.8912	likely_pathogenic	0.9165	pathogenic	-1.563	Destabilizing	0.643	D	0.756	deleterious	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.