TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26022	78289;78290;78291	chr2:178568068;178568067;178568066	chr2:179432795;179432794;179432793
N2AB	24381	73366;73367;73368	chr2:178568068;178568067;178568066	chr2:179432795;179432794;179432793
N2A	23454	70585;70586;70587	chr2:178568068;178568067;178568066	chr2:179432795;179432794;179432793
N2B	16957	51094;51095;51096	chr2:178568068;178568067;178568066	chr2:179432795;179432794;179432793
Novex-1	17082	51469;51470;51471	chr2:178568068;178568067;178568066	chr2:179432795;179432794;179432793
Novex-2	17149	51670;51671;51672	chr2:178568068;178568067;178568066	chr2:179432795;179432794;179432793
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: Fn3-77
• Domain position: 33
• Structural Position: 35
• Q(SASA): 0.2973
• 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
V/D	rs562356397	-1.39	0.667	D	0.847	0.525	0.779176552023	gnomAD-2.1.1	1.21E-05	None	None	None	None	I	None	0	0	None	0	0	None	9.81E-05	None	0	0	0
V/D	rs562356397	-1.39	0.667	D	0.847	0.525	0.779176552023	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	0	2.06954E-04	0
V/D	rs562356397	-1.39	0.667	D	0.847	0.525	0.779176552023	1000 genomes	1.99681E-04	None	None	None	None	I	None	0	0	None	None	0	0	None	None	None	1E-03	None
V/D	rs562356397	-1.39	0.667	D	0.847	0.525	0.779176552023	gnomAD-4.0.0	2.47925E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	4.39194E-05	0
V/G	None	None	0.667	N	0.841	0.509	0.744392159427	gnomAD-4.0.0	2.05312E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.69882E-06	0	0
V/I	rs374764110	-0.586	0.002	N	0.223	0.054	None	gnomAD-2.1.1	8.96E-05	None	None	None	None	I	None	4.96196E-04	2.84E-05	None	0	0	None	0	None	0	8.64E-05	1.41203E-04
V/I	rs374764110	-0.586	0.002	N	0.223	0.054	None	gnomAD-3.1.2	1.84143E-04	None	None	None	None	I	None	5.79514E-04	0	0	0	0	None	0	0	5.88E-05	0	0
V/I	rs374764110	-0.586	0.002	N	0.223	0.054	None	1000 genomes	1.99681E-04	None	None	None	None	I	None	8E-04	0	None	None	0	0	None	None	None	0	None
V/I	rs374764110	-0.586	0.002	N	0.223	0.054	None	gnomAD-4.0.0	5.45456E-05	None	None	None	None	I	None	5.20097E-04	1.66783E-05	None	0	0	None	0	1.65235E-04	3.56067E-05	1.09798E-05	6.40677E-05
V/L	rs374764110	None	0.022	N	0.44	0.116	0.326881540566	gnomAD-3.1.2	1.32E-05	None	None	None	None	I	None	0	0	0	0	0	None	0	6.32911E-03	0	0	0
V/L	rs374764110	None	0.022	N	0.44	0.116	0.326881540566	gnomAD-4.0.0	1.31428E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	6.80272E-03	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
V/A	0.878	likely_pathogenic	0.8954	pathogenic	-1.831	Destabilizing	0.104	N	0.653	neutral	N	0.505098987	None	None	I
V/C	0.9485	likely_pathogenic	0.9538	pathogenic	-1.091	Destabilizing	0.968	D	0.731	prob.delet.	None	None	None	None	I
V/D	0.9888	likely_pathogenic	0.9946	pathogenic	-2.184	Highly Destabilizing	0.667	D	0.847	deleterious	D	0.522442773	None	None	I
V/E	0.9744	likely_pathogenic	0.9851	pathogenic	-2.097	Highly Destabilizing	0.726	D	0.831	deleterious	None	None	None	None	I
V/F	0.8429	likely_pathogenic	0.8385	pathogenic	-1.286	Destabilizing	0.715	D	0.782	deleterious	N	0.503071071	None	None	I
V/G	0.9424	likely_pathogenic	0.9613	pathogenic	-2.237	Highly Destabilizing	0.667	D	0.841	deleterious	N	0.512696311	None	None	I
V/H	0.9897	likely_pathogenic	0.9936	pathogenic	-1.956	Destabilizing	0.968	D	0.822	deleterious	None	None	None	None	I
V/I	0.0647	likely_benign	0.062	benign	-0.762	Destabilizing	0.002	N	0.223	neutral	N	0.388759692	None	None	I
V/K	0.9814	likely_pathogenic	0.9872	pathogenic	-1.583	Destabilizing	0.726	D	0.832	deleterious	None	None	None	None	I
V/L	0.3786	ambiguous	0.4002	ambiguous	-0.762	Destabilizing	0.022	N	0.44	neutral	N	0.516268003	None	None	I
V/M	0.5419	ambiguous	0.5565	ambiguous	-0.493	Destabilizing	0.567	D	0.67	neutral	None	None	None	None	I
V/N	0.9185	likely_pathogenic	0.9701	pathogenic	-1.532	Destabilizing	0.89	D	0.849	deleterious	None	None	None	None	I
V/P	0.9157	likely_pathogenic	0.9338	pathogenic	-1.087	Destabilizing	0.89	D	0.823	deleterious	None	None	None	None	I
V/Q	0.9752	likely_pathogenic	0.9841	pathogenic	-1.594	Destabilizing	0.89	D	0.819	deleterious	None	None	None	None	I
V/R	0.9742	likely_pathogenic	0.9818	pathogenic	-1.144	Destabilizing	0.726	D	0.852	deleterious	None	None	None	None	I
V/S	0.9304	likely_pathogenic	0.9547	pathogenic	-2.042	Highly Destabilizing	0.726	D	0.812	deleterious	None	None	None	None	I
V/T	0.8442	likely_pathogenic	0.8725	pathogenic	-1.846	Destabilizing	0.272	N	0.726	prob.delet.	None	None	None	None	I
V/W	0.9959	likely_pathogenic	0.9962	pathogenic	-1.694	Destabilizing	0.968	D	0.785	deleterious	None	None	None	None	I
V/Y	0.9786	likely_pathogenic	0.9827	pathogenic	-1.355	Destabilizing	0.726	D	0.758	deleterious	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.