TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31962	96109;96110;96111	chr2:178544345;178544344;178544343	chr2:179409072;179409071;179409070
N2AB	30321	91186;91187;91188	chr2:178544345;178544344;178544343	chr2:179409072;179409071;179409070
N2A	29394	88405;88406;88407	chr2:178544345;178544344;178544343	chr2:179409072;179409071;179409070
N2B	22897	68914;68915;68916	chr2:178544345;178544344;178544343	chr2:179409072;179409071;179409070
Novex-1	23022	69289;69290;69291	chr2:178544345;178544344;178544343	chr2:179409072;179409071;179409070
Novex-2	23089	69490;69491;69492	chr2:178544345;178544344;178544343	chr2:179409072;179409071;179409070
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-121
• Domain position: 54
• Structural Position: 72
• Q(SASA): 0.5981
• 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
N/D	rs369087584	0.363	0.014	N	0.239	0.148	None	gnomAD-2.1.1	4.28E-05	None	None	None	None	I	None	4.54621E-04	2.83E-05	None	0	0	None	0	None	0	0	0
N/D	rs369087584	0.363	0.014	N	0.239	0.148	None	gnomAD-3.1.2	1.90549E-04	None	None	None	None	I	None	6.7548E-04	0	0	0	0	None	0	0	0	0	4.77555E-04
N/D	rs369087584	0.363	0.014	N	0.239	0.148	None	gnomAD-4.0.0	3.65621E-05	None	None	None	None	I	None	7.47484E-04	1.66711E-05	None	0	0	None	0	0	0	0	3.20215E-05
N/I	rs535943753	0.165	0.033	N	0.461	0.103	0.426787303895	gnomAD-2.1.1	3.21E-05	None	None	None	None	I	None	3.71901E-04	0	None	0	0	None	0	None	0	0	0
N/I	rs535943753	0.165	0.033	N	0.461	0.103	0.426787303895	gnomAD-3.1.2	7.88E-05	None	None	None	None	I	None	2.89464E-04	0	0	0	0	None	0	0	0	0	0
N/I	rs535943753	0.165	0.033	N	0.461	0.103	0.426787303895	1000 genomes	1.99681E-04	None	None	None	None	I	None	8E-04	0	None	None	0	0	None	None	None	0	None
N/I	rs535943753	0.165	0.033	N	0.461	0.103	0.426787303895	gnomAD-4.0.0	1.67307E-05	None	None	None	None	I	None	3.46463E-04	0	None	0	0	None	0	0	0	0	1.60051E-05

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
N/A	0.0941	likely_benign	0.1112	benign	-0.33	Destabilizing	None	N	0.189	neutral	None	None	None	None	I
N/C	0.1847	likely_benign	0.2245	benign	0.414	Stabilizing	0.497	N	0.329	neutral	None	None	None	None	I
N/D	0.1126	likely_benign	0.1123	benign	0.048	Stabilizing	0.014	N	0.239	neutral	N	0.414642358	None	None	I
N/E	0.201	likely_benign	0.2075	benign	0.02	Stabilizing	0.009	N	0.209	neutral	None	None	None	None	I
N/F	0.3776	ambiguous	0.4269	ambiguous	-0.691	Destabilizing	0.245	N	0.413	neutral	None	None	None	None	I
N/G	0.1238	likely_benign	0.1448	benign	-0.513	Destabilizing	None	N	0.161	neutral	None	None	None	None	I
N/H	0.0889	likely_benign	0.0954	benign	-0.592	Destabilizing	0.196	N	0.231	neutral	N	0.424472563	None	None	I
N/I	0.1772	likely_benign	0.193	benign	0.067	Stabilizing	0.033	N	0.461	neutral	N	0.454931543	None	None	I
N/K	0.1259	likely_benign	0.1251	benign	0.043	Stabilizing	None	N	0.171	neutral	N	0.411063335	None	None	I
N/L	0.1463	likely_benign	0.1601	benign	0.067	Stabilizing	0.009	N	0.35	neutral	None	None	None	None	I
N/M	0.1958	likely_benign	0.2144	benign	0.371	Stabilizing	0.497	N	0.328	neutral	None	None	None	None	I
N/P	0.2792	likely_benign	0.259	benign	-0.039	Destabilizing	0.085	N	0.469	neutral	None	None	None	None	I
N/Q	0.1585	likely_benign	0.1724	benign	-0.299	Destabilizing	0.002	N	0.187	neutral	None	None	None	None	I
N/R	0.1573	likely_benign	0.1662	benign	0.063	Stabilizing	0.009	N	0.247	neutral	None	None	None	None	I
N/S	0.0602	likely_benign	0.0657	benign	-0.087	Destabilizing	0.001	N	0.142	neutral	N	0.379854994	None	None	I
N/T	0.0733	likely_benign	0.0815	benign	0.025	Stabilizing	None	N	0.134	neutral	N	0.414871644	None	None	I
N/V	0.1401	likely_benign	0.1553	benign	-0.039	Destabilizing	0.009	N	0.359	neutral	None	None	None	None	I
N/W	0.5888	likely_pathogenic	0.6358	pathogenic	-0.705	Destabilizing	0.788	D	0.328	neutral	None	None	None	None	I
N/Y	0.147	likely_benign	0.1614	benign	-0.437	Destabilizing	0.196	N	0.397	neutral	N	0.470476998	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.