TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25357	76294;76295;76296	chr2:178570063;178570062;178570061	chr2:179434790;179434789;179434788
N2AB	23716	71371;71372;71373	chr2:178570063;178570062;178570061	chr2:179434790;179434789;179434788
N2A	22789	68590;68591;68592	chr2:178570063;178570062;178570061	chr2:179434790;179434789;179434788
N2B	16292	49099;49100;49101	chr2:178570063;178570062;178570061	chr2:179434790;179434789;179434788
Novex-1	16417	49474;49475;49476	chr2:178570063;178570062;178570061	chr2:179434790;179434789;179434788
Novex-2	16484	49675;49676;49677	chr2:178570063;178570062;178570061	chr2:179434790;179434789;179434788
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGT
• RefSeq wild type template codon: GCA
• Domain: Fn3-72
• Domain position: 54
• Structural Position: 72
• Q(SASA): 0.7624
• 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
R/C	rs145437410	0.003	0.984	N	0.421	0.318	None	gnomAD-2.1.1	3.22E-05	None	None	None	None	I	None	0	0	None	0	3.91586E-04	None	0	None	4.65E-05	0	0
R/C	rs145437410	0.003	0.984	N	0.421	0.318	None	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	1.93648E-04	None	0	0	0	0	0
R/C	rs145437410	0.003	0.984	N	0.421	0.318	None	1000 genomes	1.99681E-04	None	None	None	None	I	None	0	0	None	None	1E-03	0	None	None	None	0	None
R/C	rs145437410	0.003	0.984	N	0.421	0.318	None	gnomAD-4.0.0	2.54132E-05	None	None	None	None	I	None	0	0	None	0	7.59335E-04	None	3.12823E-05	0	3.39108E-06	0	1.60092E-05
R/H	rs397517703	-0.619	0.005	N	0.273	0.071	None	gnomAD-2.1.1	3.22E-05	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	0	6.24E-05	0
R/H	rs397517703	-0.619	0.005	N	0.273	0.071	None	gnomAD-3.1.2	1.97E-05	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	2.94E-05	0	0
R/H	rs397517703	-0.619	0.005	N	0.273	0.071	None	gnomAD-4.0.0	1.79761E-05	None	None	None	None	I	None	1.33579E-05	3.336E-05	None	0	0	None	0	0	2.03463E-05	2.19592E-05	0
R/P	None	None	0.705	N	0.47	0.22	0.357929162469	gnomAD-4.0.0	6.84363E-07	None	None	None	None	I	None	0	2.23674E-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
R/A	0.5451	ambiguous	0.4361	ambiguous	0.215	Stabilizing	0.035	N	0.445	neutral	None	None	None	None	I
R/C	0.2979	likely_benign	0.2218	benign	0.004	Stabilizing	0.984	D	0.421	neutral	N	0.483548011	None	None	I
R/D	0.7294	likely_pathogenic	0.6349	pathogenic	-0.243	Destabilizing	0.001	N	0.292	neutral	None	None	None	None	I
R/E	0.5354	ambiguous	0.4316	ambiguous	-0.191	Destabilizing	0.081	N	0.377	neutral	None	None	None	None	I
R/F	0.7175	likely_pathogenic	0.6081	pathogenic	-0.068	Destabilizing	0.38	N	0.413	neutral	None	None	None	None	I
R/G	0.3373	likely_benign	0.2405	benign	0.061	Stabilizing	0.001	N	0.267	neutral	N	0.471053001	None	None	I
R/H	0.1428	likely_benign	0.1091	benign	-0.564	Destabilizing	0.005	N	0.273	neutral	N	0.488620042	None	None	I
R/I	0.4954	ambiguous	0.3979	ambiguous	0.577	Stabilizing	0.555	D	0.435	neutral	None	None	None	None	I
R/K	0.1167	likely_benign	0.1047	benign	0.101	Stabilizing	0.067	N	0.375	neutral	None	None	None	None	I
R/L	0.429	ambiguous	0.326	benign	0.577	Stabilizing	0.251	N	0.471	neutral	N	0.493121784	None	None	I
R/M	0.4733	ambiguous	0.3696	ambiguous	0.034	Stabilizing	0.935	D	0.419	neutral	None	None	None	None	I
R/N	0.6021	likely_pathogenic	0.4859	ambiguous	0.217	Stabilizing	0.081	N	0.407	neutral	None	None	None	None	I
R/P	0.7839	likely_pathogenic	0.7091	pathogenic	0.475	Stabilizing	0.705	D	0.47	neutral	N	0.463385705	None	None	I
R/Q	0.1479	likely_benign	0.1162	benign	0.194	Stabilizing	0.38	N	0.423	neutral	None	None	None	None	I
R/S	0.6058	likely_pathogenic	0.4817	ambiguous	0.091	Stabilizing	0.251	N	0.509	neutral	N	0.455062041	None	None	I
R/T	0.4059	ambiguous	0.3006	benign	0.251	Stabilizing	0.149	N	0.493	neutral	None	None	None	None	I
R/V	0.5308	ambiguous	0.4298	ambiguous	0.475	Stabilizing	0.555	D	0.462	neutral	None	None	None	None	I
R/W	0.342	ambiguous	0.2521	benign	-0.277	Destabilizing	0.935	D	0.475	neutral	None	None	None	None	I
R/Y	0.5064	ambiguous	0.4113	ambiguous	0.14	Stabilizing	0.235	N	0.457	neutral	None	None	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.