TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6755	20488;20489;20490	chr2:178727102;178727101;178727100	chr2:179591829;179591828;179591827
N2AB	6438	19537;19538;19539	chr2:178727102;178727101;178727100	chr2:179591829;179591828;179591827
N2A	5511	16756;16757;16758	chr2:178727102;178727101;178727100	chr2:179591829;179591828;179591827
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-51
• Domain position: 89
• Structural Position: 174
• Q(SASA): 0.1719
• 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	rs2079471482	None	0.722	N	0.662	0.371	0.497547018531	gnomAD-4.0.0	1.43747E-06	None	None	None	None	N	None	6.36983E-05	0	None	0	0	None	0	0	0	0	0
V/F	rs876657599	None	0.018	N	0.563	0.233	0.482646159919	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/F	rs876657599	None	0.018	N	0.563	0.233	0.482646159919	gnomAD-4.0.0	2.71075E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.07908E-06	0	0
V/I	None	-0.473	0.008	N	0.282	0.071	0.19670166235	gnomAD-2.1.1	4.29E-06	None	None	None	None	N	None	6.7E-05	0	None	0	0	None	0	None	0	0	0
V/I	None	-0.473	0.008	N	0.282	0.071	0.19670166235	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
V/I	None	-0.473	0.008	N	0.282	0.071	0.19670166235	gnomAD-4.0.0	6.57583E-06	None	None	None	None	N	None	2.41371E-05	0	None	0	0	None	0	0	0	0	0
V/L	rs876657599	None	0.003	N	0.291	0.145	0.0884992946249	gnomAD-2.1.1	4.29E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.69E-05	None	0	0	0
V/L	rs876657599	None	0.003	N	0.291	0.145	0.0884992946249	gnomAD-4.0.0	1.70727E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.6429E-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	0.6756	likely_pathogenic	0.727	pathogenic	-2.371	Highly Destabilizing	0.722	D	0.662	neutral	N	0.495795553	None	None	N
V/C	0.9203	likely_pathogenic	0.9273	pathogenic	-2.012	Highly Destabilizing	0.996	D	0.81	deleterious	None	None	None	None	N
V/D	0.9703	likely_pathogenic	0.9834	pathogenic	-2.977	Highly Destabilizing	0.983	D	0.875	deleterious	N	0.496302532	None	None	N
V/E	0.9301	likely_pathogenic	0.9511	pathogenic	-2.729	Highly Destabilizing	0.961	D	0.856	deleterious	None	None	None	None	N
V/F	0.2389	likely_benign	0.2708	benign	-1.415	Destabilizing	0.018	N	0.563	neutral	N	0.463105762	None	None	N
V/G	0.7891	likely_pathogenic	0.8321	pathogenic	-2.943	Highly Destabilizing	0.949	D	0.857	deleterious	N	0.496302532	None	None	N
V/H	0.9635	likely_pathogenic	0.9763	pathogenic	-2.665	Highly Destabilizing	0.996	D	0.867	deleterious	None	None	None	None	N
V/I	0.071	likely_benign	0.0763	benign	-0.75	Destabilizing	0.008	N	0.282	neutral	N	0.459347567	None	None	N
V/K	0.9613	likely_pathogenic	0.9738	pathogenic	-1.968	Destabilizing	0.961	D	0.849	deleterious	None	None	None	None	N
V/L	0.1519	likely_benign	0.1765	benign	-0.75	Destabilizing	0.003	N	0.291	neutral	N	0.36170551	None	None	N
V/M	0.1969	likely_benign	0.2158	benign	-0.89	Destabilizing	0.923	D	0.71	prob.delet.	None	None	None	None	N
V/N	0.9129	likely_pathogenic	0.9457	pathogenic	-2.385	Highly Destabilizing	0.987	D	0.857	deleterious	None	None	None	None	N
V/P	0.9806	likely_pathogenic	0.9903	pathogenic	-1.266	Destabilizing	0.987	D	0.85	deleterious	None	None	None	None	N
V/Q	0.9308	likely_pathogenic	0.9528	pathogenic	-2.175	Highly Destabilizing	0.987	D	0.846	deleterious	None	None	None	None	N
V/R	0.9428	likely_pathogenic	0.9615	pathogenic	-1.834	Destabilizing	0.961	D	0.86	deleterious	None	None	None	None	N
V/S	0.8796	likely_pathogenic	0.9138	pathogenic	-3.036	Highly Destabilizing	0.961	D	0.837	deleterious	None	None	None	None	N
V/T	0.7697	likely_pathogenic	0.8126	pathogenic	-2.635	Highly Destabilizing	0.775	D	0.695	prob.neutral	None	None	None	None	N
V/W	0.9098	likely_pathogenic	0.9363	pathogenic	-1.933	Destabilizing	0.996	D	0.865	deleterious	None	None	None	None	N
V/Y	0.7595	likely_pathogenic	0.8133	pathogenic	-1.591	Destabilizing	0.858	D	0.824	deleterious	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.