TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25050	75373;75374;75375	chr2:178570984;178570983;178570982	chr2:179435711;179435710;179435709
N2AB	23409	70450;70451;70452	chr2:178570984;178570983;178570982	chr2:179435711;179435710;179435709
N2A	22482	67669;67670;67671	chr2:178570984;178570983;178570982	chr2:179435711;179435710;179435709
N2B	15985	48178;48179;48180	chr2:178570984;178570983;178570982	chr2:179435711;179435710;179435709
Novex-1	16110	48553;48554;48555	chr2:178570984;178570983;178570982	chr2:179435711;179435710;179435709
Novex-2	16177	48754;48755;48756	chr2:178570984;178570983;178570982	chr2:179435711;179435710;179435709
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-70
• Domain position: 45
• Structural Position: 60
• Q(SASA): 0.3636
• 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
E/K	rs770754919	-0.096	0.012	N	0.258	0.077	0.191931220699	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	5.8E-05	None	0	0	None	0	None	0	0	0
E/K	rs770754919	-0.096	0.012	N	0.258	0.077	0.191931220699	gnomAD-4.0.0	3.18384E-06	None	None	None	None	N	None	0	4.57289E-05	None	0	0	None	0	0	0	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
E/A	0.1232	likely_benign	0.1316	benign	-0.002	Destabilizing	0.012	N	0.281	neutral	N	0.47134379	None	None	N
E/C	0.7306	likely_pathogenic	0.7348	pathogenic	-0.324	Destabilizing	0.864	D	0.289	neutral	None	None	None	None	N
E/D	0.0634	likely_benign	0.0643	benign	-0.487	Destabilizing	None	N	0.087	neutral	N	0.412756846	None	None	N
E/F	0.6429	likely_pathogenic	0.6363	pathogenic	-0.108	Destabilizing	0.628	D	0.295	neutral	None	None	None	None	N
E/G	0.1128	likely_benign	0.1195	benign	-0.084	Destabilizing	0.024	N	0.219	neutral	N	0.444925193	None	None	N
E/H	0.3568	ambiguous	0.3634	ambiguous	0.574	Stabilizing	0.356	N	0.197	neutral	None	None	None	None	N
E/I	0.3791	ambiguous	0.3772	ambiguous	0.153	Stabilizing	0.356	N	0.334	neutral	None	None	None	None	N
E/K	0.1714	likely_benign	0.1698	benign	0.293	Stabilizing	0.012	N	0.258	neutral	N	0.489966836	None	None	N
E/L	0.3379	likely_benign	0.3421	ambiguous	0.153	Stabilizing	0.072	N	0.264	neutral	None	None	None	None	N
E/M	0.4146	ambiguous	0.4271	ambiguous	-0.12	Destabilizing	0.356	N	0.263	neutral	None	None	None	None	N
E/N	0.1255	likely_benign	0.1359	benign	0.088	Stabilizing	None	N	0.081	neutral	None	None	None	None	N
E/P	0.5848	likely_pathogenic	0.5531	ambiguous	0.118	Stabilizing	0.136	N	0.295	neutral	None	None	None	None	N
E/Q	0.15	likely_benign	0.1522	benign	0.077	Stabilizing	0.001	N	0.186	neutral	N	0.505187004	None	None	N
E/R	0.2684	likely_benign	0.2605	benign	0.526	Stabilizing	0.038	N	0.15	neutral	None	None	None	None	N
E/S	0.1183	likely_benign	0.1267	benign	-0.04	Destabilizing	0.001	N	0.103	neutral	None	None	None	None	N
E/T	0.174	likely_benign	0.187	benign	0.038	Stabilizing	0.016	N	0.249	neutral	None	None	None	None	N
E/V	0.2244	likely_benign	0.2293	benign	0.118	Stabilizing	0.055	N	0.255	neutral	N	0.513691844	None	None	N
E/W	0.8274	likely_pathogenic	0.8118	pathogenic	-0.095	Destabilizing	0.864	D	0.324	neutral	None	None	None	None	N
E/Y	0.5002	ambiguous	0.4946	ambiguous	0.102	Stabilizing	0.628	D	0.273	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.