TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16693	50302;50303;50304	chr2:178612448;178612447;178612446	chr2:179477175;179477174;179477173
N2AB	15052	45379;45380;45381	chr2:178612448;178612447;178612446	chr2:179477175;179477174;179477173
N2A	14125	42598;42599;42600	chr2:178612448;178612447;178612446	chr2:179477175;179477174;179477173
N2B	7628	23107;23108;23109	chr2:178612448;178612447;178612446	chr2:179477175;179477174;179477173
Novex-1	7753	23482;23483;23484	chr2:178612448;178612447;178612446	chr2:179477175;179477174;179477173
Novex-2	7820	23683;23684;23685	chr2:178612448;178612447;178612446	chr2:179477175;179477174;179477173
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Fn3-9
• Domain position: 43
• Structural Position: 50
• Q(SASA): 0.3396
• 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	rs927020149	-1.364	0.099	N	0.235	0.162	0.392855499163	gnomAD-2.1.1	4.06E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.02E-06	0
V/A	rs927020149	-1.364	0.099	N	0.235	0.162	0.392855499163	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
V/A	rs927020149	-1.364	0.099	N	0.235	0.162	0.392855499163	gnomAD-4.0.0	5.58201E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.63236E-06	0	0
V/I	rs377141765	-0.524	0.906	N	0.503	0.162	None	gnomAD-2.1.1	2.16E-05	None	None	None	None	N	None	0	2.84E-05	None	9.75E-05	0	None	3.27E-05	None	0	2.38E-05	0
V/I	rs377141765	-0.524	0.906	N	0.503	0.162	None	gnomAD-3.1.2	3.29E-05	None	None	None	None	N	None	0	6.56E-05	0	0	0	None	0	0	4.42E-05	2.07211E-04	0
V/I	rs377141765	-0.524	0.906	N	0.503	0.162	None	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	0	None	None	0	0	None	None	None	1E-03	None
V/I	rs377141765	-0.524	0.906	N	0.503	0.162	None	gnomAD-4.0.0	3.53491E-05	None	None	None	None	N	None	0	3.33823E-05	None	3.38112E-05	0	None	0	0	4.49461E-05	1.09844E-05	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	0.6582	likely_pathogenic	0.5753	pathogenic	-1.166	Destabilizing	0.099	N	0.235	neutral	N	0.47347114	None	None	N
V/C	0.9404	likely_pathogenic	0.9287	pathogenic	-0.844	Destabilizing	0.999	D	0.604	neutral	None	None	None	None	N
V/D	0.9489	likely_pathogenic	0.9523	pathogenic	-0.632	Destabilizing	0.983	D	0.727	prob.delet.	N	0.465256544	None	None	N
V/E	0.871	likely_pathogenic	0.8858	pathogenic	-0.675	Destabilizing	0.987	D	0.687	prob.neutral	None	None	None	None	N
V/F	0.7225	likely_pathogenic	0.6904	pathogenic	-0.938	Destabilizing	0.987	D	0.587	neutral	D	0.544432496	None	None	N
V/G	0.7552	likely_pathogenic	0.7202	pathogenic	-1.425	Destabilizing	0.967	D	0.661	neutral	N	0.485048323	None	None	N
V/H	0.9664	likely_pathogenic	0.9631	pathogenic	-0.843	Destabilizing	0.999	D	0.733	prob.delet.	None	None	None	None	N
V/I	0.1331	likely_benign	0.1107	benign	-0.583	Destabilizing	0.906	D	0.503	neutral	N	0.4842543	None	None	N
V/K	0.8965	likely_pathogenic	0.9112	pathogenic	-0.884	Destabilizing	0.987	D	0.675	prob.neutral	None	None	None	None	N
V/L	0.7151	likely_pathogenic	0.6272	pathogenic	-0.583	Destabilizing	0.062	N	0.235	neutral	N	0.481954699	None	None	N
V/M	0.5607	ambiguous	0.468	ambiguous	-0.47	Destabilizing	0.975	D	0.587	neutral	None	None	None	None	N
V/N	0.8577	likely_pathogenic	0.819	pathogenic	-0.621	Destabilizing	0.996	D	0.732	prob.delet.	None	None	None	None	N
V/P	0.915	likely_pathogenic	0.9156	pathogenic	-0.741	Destabilizing	0.987	D	0.701	prob.neutral	None	None	None	None	N
V/Q	0.8579	likely_pathogenic	0.8555	pathogenic	-0.837	Destabilizing	0.996	D	0.712	prob.delet.	None	None	None	None	N
V/R	0.8771	likely_pathogenic	0.9095	pathogenic	-0.343	Destabilizing	0.987	D	0.733	prob.delet.	None	None	None	None	N
V/S	0.7056	likely_pathogenic	0.6508	pathogenic	-1.168	Destabilizing	0.95	D	0.61	neutral	None	None	None	None	N
V/T	0.6028	likely_pathogenic	0.5245	ambiguous	-1.105	Destabilizing	0.916	D	0.525	neutral	None	None	None	None	N
V/W	0.9879	likely_pathogenic	0.9875	pathogenic	-1.027	Destabilizing	0.999	D	0.721	prob.delet.	None	None	None	None	N
V/Y	0.9444	likely_pathogenic	0.9442	pathogenic	-0.756	Destabilizing	0.987	D	0.599	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.