TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28134	84625;84626;84627	chr2:178561732;178561731;178561730	chr2:179426459;179426458;179426457
N2AB	26493	79702;79703;79704	chr2:178561732;178561731;178561730	chr2:179426459;179426458;179426457
N2A	25566	76921;76922;76923	chr2:178561732;178561731;178561730	chr2:179426459;179426458;179426457
N2B	19069	57430;57431;57432	chr2:178561732;178561731;178561730	chr2:179426459;179426458;179426457
Novex-1	19194	57805;57806;57807	chr2:178561732;178561731;178561730	chr2:179426459;179426458;179426457
Novex-2	19261	58006;58007;58008	chr2:178561732;178561731;178561730	chr2:179426459;179426458;179426457
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGC
• RefSeq wild type template codon: GCG
• Domain: Fn3-92
• Domain position: 80
• Structural Position: 113
• Q(SASA): 0.7145
• 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	rs771002170	0.011	1.0	N	0.651	0.424	0.608144913684	gnomAD-2.1.1	3.94E-05	None	None	None	None	I	None	8.27E-05	1.98615E-04	None	9.72E-05	0	None	0	None	0	0	1.41163E-04
R/C	rs771002170	0.011	1.0	N	0.651	0.424	0.608144913684	gnomAD-3.1.2	1.31E-05	None	None	None	None	I	None	2.41E-05	6.55E-05	0	0	0	None	0	0	0	0	0
R/C	rs771002170	0.011	1.0	N	0.651	0.424	0.608144913684	gnomAD-4.0.0	1.67469E-05	None	None	None	None	I	None	2.6738E-05	1.50311E-04	None	3.38203E-05	2.23354E-05	None	1.56436E-05	0	5.93767E-06	2.19746E-05	6.41169E-05
R/H	rs777785413	-0.656	0.997	N	0.514	0.398	0.299427821978	gnomAD-2.1.1	1.21E-05	None	None	None	None	I	None	0	2.91E-05	None	0	0	None	3.29E-05	None	4.68E-05	0	0
R/H	rs777785413	-0.656	0.997	N	0.514	0.398	0.299427821978	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
R/H	rs777785413	-0.656	0.997	N	0.514	0.398	0.299427821978	gnomAD-4.0.0	6.82345E-06	None	None	None	None	I	None	1.33633E-05	3.34124E-05	None	0	0	None	1.56411E-05	0	3.3932E-06	2.19891E-05	1.60282E-05
R/L	rs777785413	0.581	0.954	N	0.483	0.417	0.481543764896	gnomAD-2.1.1	8.08E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	1.79E-05	0
R/L	rs777785413	0.581	0.954	N	0.483	0.417	0.481543764896	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
R/L	rs777785413	0.581	0.954	N	0.483	0.417	0.481543764896	gnomAD-4.0.0	5.58282E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	6.7864E-06	0	1.60282E-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
R/A	0.9347	likely_pathogenic	0.9344	pathogenic	0.086	Stabilizing	0.916	D	0.57	neutral	None	None	None	None	I
R/C	0.5938	likely_pathogenic	0.7922	pathogenic	-0.116	Destabilizing	1.0	D	0.651	neutral	N	0.50702109	None	None	I
R/D	0.9829	likely_pathogenic	0.9839	pathogenic	-0.231	Destabilizing	0.975	D	0.472	neutral	None	None	None	None	I
R/E	0.9256	likely_pathogenic	0.9335	pathogenic	-0.163	Destabilizing	0.845	D	0.536	neutral	None	None	None	None	I
R/F	0.9532	likely_pathogenic	0.9673	pathogenic	-0.191	Destabilizing	0.996	D	0.587	neutral	None	None	None	None	I
R/G	0.9097	likely_pathogenic	0.9192	pathogenic	-0.093	Destabilizing	0.954	D	0.483	neutral	N	0.464168946	None	None	I
R/H	0.434	ambiguous	0.4877	ambiguous	-0.825	Destabilizing	0.997	D	0.514	neutral	N	0.481661906	None	None	I
R/I	0.7556	likely_pathogenic	0.7898	pathogenic	0.517	Stabilizing	0.987	D	0.587	neutral	None	None	None	None	I
R/K	0.3392	likely_benign	0.3568	ambiguous	-0.016	Destabilizing	0.693	D	0.49	neutral	None	None	None	None	I
R/L	0.7585	likely_pathogenic	0.779	pathogenic	0.517	Stabilizing	0.954	D	0.483	neutral	N	0.52119382	None	None	I
R/M	0.8495	likely_pathogenic	0.882	pathogenic	-0.023	Destabilizing	0.997	D	0.513	neutral	None	None	None	None	I
R/N	0.9611	likely_pathogenic	0.9651	pathogenic	0.079	Stabilizing	0.975	D	0.494	neutral	None	None	None	None	I
R/P	0.9434	likely_pathogenic	0.9389	pathogenic	0.393	Stabilizing	0.993	D	0.553	neutral	N	0.519308308	None	None	I
R/Q	0.4214	ambiguous	0.45	ambiguous	0.068	Stabilizing	0.253	N	0.448	neutral	None	None	None	None	I
R/S	0.9559	likely_pathogenic	0.9606	pathogenic	-0.109	Destabilizing	0.954	D	0.542	neutral	N	0.497354168	None	None	I
R/T	0.8879	likely_pathogenic	0.8997	pathogenic	0.089	Stabilizing	0.975	D	0.5	neutral	None	None	None	None	I
R/V	0.8757	likely_pathogenic	0.8883	pathogenic	0.393	Stabilizing	0.975	D	0.577	neutral	None	None	None	None	I
R/W	0.6178	likely_pathogenic	0.719	pathogenic	-0.363	Destabilizing	0.999	D	0.661	neutral	None	None	None	None	I
R/Y	0.8475	likely_pathogenic	0.8846	pathogenic	0.064	Stabilizing	0.996	D	0.562	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.