TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14775	44548;44549;44550	chr2:178629402;178629401;178629400	chr2:179494129;179494128;179494127
N2AB	13134	39625;39626;39627	chr2:178629402;178629401;178629400	chr2:179494129;179494128;179494127
N2A	12207	36844;36845;36846	chr2:178629402;178629401;178629400	chr2:179494129;179494128;179494127
N2B	5710	17353;17354;17355	chr2:178629402;178629401;178629400	chr2:179494129;179494128;179494127
Novex-1	5835	17728;17729;17730	chr2:178629402;178629401;178629400	chr2:179494129;179494128;179494127
Novex-2	5902	17929;17930;17931	chr2:178629402;178629401;178629400	chr2:179494129;179494128;179494127
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-99
• Domain position: 11
• Structural Position: 16
• Q(SASA): 0.2942
• 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
V/A	None	None	0.999	N	0.482	0.638	0.715797810027	gnomAD-4.0.0	1.59311E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86179E-06	0	0
V/L	rs540115992	-0.485	0.999	D	0.513	0.575	0.680116873462	gnomAD-2.1.1	2.82E-05	None	None	None	None	N	None	0	2.03276E-04	None	0	0	None	0	None	0	0	0
V/L	rs540115992	-0.485	0.999	D	0.513	0.575	0.680116873462	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	0	1.96464E-04	0	0	0	None	0	0	0	0	0
V/L	rs540115992	-0.485	0.999	D	0.513	0.575	0.680116873462	gnomAD-4.0.0	6.82023E-06	None	None	None	None	N	None	0	1.83462E-04	None	0	0	None	0	0	0	0	0
V/M	rs540115992	-0.509	1.0	D	0.73	0.633	0.731815193843	gnomAD-2.1.1	8.94E-05	None	None	None	None	N	None	8.27E-05	6.23512E-04	None	0	0	None	0	None	0	7.82E-06	0
V/M	rs540115992	-0.509	1.0	D	0.73	0.633	0.731815193843	gnomAD-3.1.2	2.63E-05	None	None	None	None	N	None	2.41E-05	1.96464E-04	0	0	0	None	0	0	0	0	0
V/M	rs540115992	-0.509	1.0	D	0.73	0.633	0.731815193843	1000 genomes	3.99361E-04	None	None	None	None	N	None	1.5E-03	0	None	None	0	0	None	None	None	0	None
V/M	rs540115992	-0.509	1.0	D	0.73	0.633	0.731815193843	gnomAD-4.0.0	2.04592E-05	None	None	None	None	N	None	1.3338E-05	4.66838E-04	None	0	2.23784E-05	None	0	0	2.54387E-06	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
V/A	0.4804	ambiguous	0.4509	ambiguous	-0.873	Destabilizing	0.999	D	0.482	neutral	N	0.518003372	None	None	N
V/C	0.9259	likely_pathogenic	0.921	pathogenic	-0.759	Destabilizing	1.0	D	0.636	neutral	None	None	None	None	N
V/D	0.9787	likely_pathogenic	0.9801	pathogenic	-0.433	Destabilizing	1.0	D	0.684	prob.neutral	None	None	None	None	N
V/E	0.9302	likely_pathogenic	0.9311	pathogenic	-0.514	Destabilizing	1.0	D	0.649	neutral	D	0.701391176	None	None	N
V/F	0.8219	likely_pathogenic	0.8511	pathogenic	-0.893	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
V/G	0.7285	likely_pathogenic	0.7411	pathogenic	-1.072	Destabilizing	1.0	D	0.673	neutral	D	0.701306191	None	None	N
V/H	0.9853	likely_pathogenic	0.9849	pathogenic	-0.623	Destabilizing	1.0	D	0.646	neutral	None	None	None	None	N
V/I	0.1592	likely_benign	0.155	benign	-0.476	Destabilizing	0.998	D	0.516	neutral	None	None	None	None	N
V/K	0.9098	likely_pathogenic	0.9145	pathogenic	-0.721	Destabilizing	1.0	D	0.645	neutral	None	None	None	None	N
V/L	0.656	likely_pathogenic	0.6447	pathogenic	-0.476	Destabilizing	0.999	D	0.513	neutral	D	0.585164987	None	None	N
V/M	0.5571	ambiguous	0.5807	pathogenic	-0.454	Destabilizing	1.0	D	0.73	prob.delet.	D	0.700319646	None	None	N
V/N	0.9445	likely_pathogenic	0.9537	pathogenic	-0.448	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
V/P	0.9901	likely_pathogenic	0.9925	pathogenic	-0.572	Destabilizing	1.0	D	0.655	neutral	None	None	None	None	N
V/Q	0.9152	likely_pathogenic	0.915	pathogenic	-0.67	Destabilizing	1.0	D	0.659	neutral	None	None	None	None	N
V/R	0.8937	likely_pathogenic	0.8942	pathogenic	-0.208	Destabilizing	1.0	D	0.676	prob.neutral	None	None	None	None	N
V/S	0.7846	likely_pathogenic	0.7578	pathogenic	-0.888	Destabilizing	1.0	D	0.656	neutral	None	None	None	None	N
V/T	0.5625	ambiguous	0.5599	ambiguous	-0.861	Destabilizing	0.999	D	0.657	neutral	None	None	None	None	N
V/W	0.9976	likely_pathogenic	0.9973	pathogenic	-0.979	Destabilizing	1.0	D	0.643	neutral	None	None	None	None	N
V/Y	0.982	likely_pathogenic	0.9843	pathogenic	-0.69	Destabilizing	1.0	D	0.694	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.