TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27761	83506;83507;83508	chr2:178562851;178562850;178562849	chr2:179427578;179427577;179427576
N2AB	26120	78583;78584;78585	chr2:178562851;178562850;178562849	chr2:179427578;179427577;179427576
N2A	25193	75802;75803;75804	chr2:178562851;178562850;178562849	chr2:179427578;179427577;179427576
N2B	18696	56311;56312;56313	chr2:178562851;178562850;178562849	chr2:179427578;179427577;179427576
Novex-1	18821	56686;56687;56688	chr2:178562851;178562850;178562849	chr2:179427578;179427577;179427576
Novex-2	18888	56887;56888;56889	chr2:178562851;178562850;178562849	chr2:179427578;179427577;179427576
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: Ig-141
• Domain position: 86
• Structural Position: 174
• Q(SASA): 0.1554
• 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/I	rs371788070	-0.383	0.999	N	0.539	0.288	None	gnomAD-2.1.1	1.62027E-04	None	None	None	None	N	None	1.2499E-04	0	None	0	0	None	0	None	0	3.23533E-04	1.41603E-04
V/I	rs371788070	-0.383	0.999	N	0.539	0.288	None	gnomAD-3.1.2	1.90692E-04	None	None	None	None	N	None	2.41429E-04	0	0	0	0	None	0	0	2.79338E-04	0	0
V/I	rs371788070	-0.383	0.999	N	0.539	0.288	None	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	0	None	None	0	1E-03	None	None	None	0	None
V/I	rs371788070	-0.383	0.999	N	0.539	0.288	None	gnomAD-4.0.0	3.53407E-04	None	None	None	None	N	None	2.66667E-04	0	None	0	0	None	0	0	4.54453E-04	0	2.2433E-04
V/L	rs371788070	-0.385	0.999	N	0.643	0.337	None	gnomAD-2.1.1	8.28E-05	None	None	None	None	N	None	4.17E-05	5.7E-05	None	1.9478E-04	0	None	0	None	0	1.42039E-04	0
V/L	rs371788070	-0.385	0.999	N	0.643	0.337	None	gnomAD-3.1.2	5.92E-05	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	1.17616E-04	0	0
V/L	rs371788070	-0.385	0.999	N	0.643	0.337	None	gnomAD-4.0.0	1.32692E-04	None	None	None	None	N	None	2.67101E-05	3.34113E-05	None	6.7627E-05	0	None	0	0	1.72962E-04	0	6.41169E-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
V/A	0.9456	likely_pathogenic	0.9483	pathogenic	-2.176	Highly Destabilizing	0.999	D	0.622	neutral	D	0.533485321	None	None	N
V/C	0.9706	likely_pathogenic	0.9702	pathogenic	-1.882	Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	N
V/D	0.9996	likely_pathogenic	0.9996	pathogenic	-2.68	Highly Destabilizing	1.0	D	0.862	deleterious	D	0.5339923	None	None	N
V/E	0.9985	likely_pathogenic	0.9985	pathogenic	-2.434	Highly Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	N
V/F	0.9627	likely_pathogenic	0.9569	pathogenic	-1.29	Destabilizing	1.0	D	0.831	deleterious	N	0.521368547	None	None	N
V/G	0.9732	likely_pathogenic	0.9757	pathogenic	-2.758	Highly Destabilizing	1.0	D	0.864	deleterious	D	0.5339923	None	None	N
V/H	0.9995	likely_pathogenic	0.9995	pathogenic	-2.534	Highly Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
V/I	0.1764	likely_benign	0.1526	benign	-0.54	Destabilizing	0.999	D	0.539	neutral	N	0.480788263	None	None	N
V/K	0.9984	likely_pathogenic	0.9985	pathogenic	-1.866	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
V/L	0.8596	likely_pathogenic	0.8254	pathogenic	-0.54	Destabilizing	0.999	D	0.643	neutral	N	0.443464348	None	None	N
V/M	0.9151	likely_pathogenic	0.9068	pathogenic	-0.687	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	N
V/N	0.9979	likely_pathogenic	0.9979	pathogenic	-2.249	Highly Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
V/P	0.9982	likely_pathogenic	0.9984	pathogenic	-1.058	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
V/Q	0.9982	likely_pathogenic	0.9983	pathogenic	-2.032	Highly Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
V/R	0.9969	likely_pathogenic	0.9971	pathogenic	-1.764	Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
V/S	0.9904	likely_pathogenic	0.9909	pathogenic	-2.925	Highly Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	N
V/T	0.949	likely_pathogenic	0.9521	pathogenic	-2.517	Highly Destabilizing	0.999	D	0.658	neutral	None	None	None	None	N
V/W	0.9997	likely_pathogenic	0.9996	pathogenic	-1.811	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
V/Y	0.9975	likely_pathogenic	0.9974	pathogenic	-1.429	Destabilizing	1.0	D	0.827	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.