TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25927	78004;78005;78006	chr2:178568353;178568352;178568351	chr2:179433080;179433079;179433078
N2AB	24286	73081;73082;73083	chr2:178568353;178568352;178568351	chr2:179433080;179433079;179433078
N2A	23359	70300;70301;70302	chr2:178568353;178568352;178568351	chr2:179433080;179433079;179433078
N2B	16862	50809;50810;50811	chr2:178568353;178568352;178568351	chr2:179433080;179433079;179433078
Novex-1	16987	51184;51185;51186	chr2:178568353;178568352;178568351	chr2:179433080;179433079;179433078
Novex-2	17054	51385;51386;51387	chr2:178568353;178568352;178568351	chr2:179433080;179433079;179433078
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-76
• Domain position: 38
• Structural Position: 39
• Q(SASA): 0.1388
• 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	rs780196850	-1.403	0.025	N	0.427	0.094	None	gnomAD-2.1.1	1.79E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	3.91E-05	0
I/L	rs780196850	-1.403	0.025	N	0.427	0.094	None	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
I/L	rs780196850	-1.403	0.025	N	0.427	0.094	None	gnomAD-4.0.0	4.52491E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.0864E-05	0	2.08247E-04
I/M	rs1226545466	-1.713	0.497	N	0.647	0.203	0.423480098753	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
I/M	rs1226545466	-1.713	0.497	N	0.647	0.203	0.423480098753	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
I/M	rs1226545466	-1.713	0.497	N	0.647	0.203	0.423480098753	gnomAD-4.0.0	1.11574E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.52592E-05	0	0
I/T	rs905403082	-2.947	0.124	N	0.595	0.269	0.549545986626	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.88E-06	0
I/T	rs905403082	-2.947	0.124	N	0.595	0.269	0.549545986626	gnomAD-4.0.0	2.05314E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79919E-06	0	1.65739E-05
I/V	rs780196850	-1.938	None	N	0.241	0.064	0.467585353272	gnomAD-2.1.1	2.14E-05	None	None	None	None	N	None	4.14E-05	0	None	0	0	None	0	None	0	3.91E-05	0
I/V	rs780196850	-1.938	None	N	0.241	0.064	0.467585353272	gnomAD-3.1.2	2.63E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	5.88E-05	0	0
I/V	rs780196850	-1.938	None	N	0.241	0.064	0.467585353272	gnomAD-4.0.0	1.98352E-05	None	None	None	None	N	None	1.33511E-05	0	None	0	0	None	0	0	2.62797E-05	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	0.5221	ambiguous	0.5829	pathogenic	-2.837	Highly Destabilizing	0.072	N	0.567	neutral	None	None	None	None	N
I/C	0.7746	likely_pathogenic	0.8	pathogenic	-2.15	Highly Destabilizing	0.909	D	0.673	neutral	None	None	None	None	N
I/D	0.9507	likely_pathogenic	0.9633	pathogenic	-3.203	Highly Destabilizing	0.726	D	0.717	prob.delet.	None	None	None	None	N
I/E	0.8692	likely_pathogenic	0.8913	pathogenic	-3.025	Highly Destabilizing	0.726	D	0.706	prob.neutral	None	None	None	None	N
I/F	0.3134	likely_benign	0.401	ambiguous	-1.723	Destabilizing	0.497	N	0.628	neutral	N	0.478014602	None	None	N
I/G	0.8981	likely_pathogenic	0.9244	pathogenic	-3.318	Highly Destabilizing	0.726	D	0.696	prob.neutral	None	None	None	None	N
I/H	0.68	likely_pathogenic	0.7503	pathogenic	-2.577	Highly Destabilizing	0.968	D	0.73	prob.delet.	None	None	None	None	N
I/K	0.5607	ambiguous	0.633	pathogenic	-2.23	Highly Destabilizing	0.726	D	0.707	prob.neutral	None	None	None	None	N
I/L	0.2304	likely_benign	0.2676	benign	-1.453	Destabilizing	0.025	N	0.427	neutral	N	0.467201275	None	None	N
I/M	0.1649	likely_benign	0.1888	benign	-1.424	Destabilizing	0.497	N	0.647	neutral	N	0.497702246	None	None	N
I/N	0.5926	likely_pathogenic	0.66	pathogenic	-2.477	Highly Destabilizing	0.859	D	0.731	prob.delet.	N	0.521807109	None	None	N
I/P	0.9933	likely_pathogenic	0.9955	pathogenic	-1.897	Destabilizing	0.89	D	0.718	prob.delet.	None	None	None	None	N
I/Q	0.684	likely_pathogenic	0.7263	pathogenic	-2.44	Highly Destabilizing	0.89	D	0.74	deleterious	None	None	None	None	N
I/R	0.4551	ambiguous	0.5317	ambiguous	-1.736	Destabilizing	0.726	D	0.732	prob.delet.	None	None	None	None	N
I/S	0.5077	ambiguous	0.5649	pathogenic	-3.133	Highly Destabilizing	0.497	N	0.655	neutral	N	0.468553947	None	None	N
I/T	0.2042	likely_benign	0.2296	benign	-2.831	Highly Destabilizing	0.124	N	0.595	neutral	N	0.487329176	None	None	N
I/V	0.07	likely_benign	0.0694	benign	-1.897	Destabilizing	None	N	0.241	neutral	N	0.453544676	None	None	N
I/W	0.8964	likely_pathogenic	0.9189	pathogenic	-2.047	Highly Destabilizing	0.968	D	0.723	prob.delet.	None	None	None	None	N
I/Y	0.7318	likely_pathogenic	0.7877	pathogenic	-1.854	Destabilizing	0.726	D	0.679	prob.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.