TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7085	21478;21479;21480	chr2:178724006;178724005;178724004	chr2:179588733;179588732;179588731
N2AB	6768	20527;20528;20529	chr2:178724006;178724005;178724004	chr2:179588733;179588732;179588731
N2A	5841	17746;17747;17748	chr2:178724006;178724005;178724004	chr2:179588733;179588732;179588731
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: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-55
• Domain position: 42
• Structural Position: 59
• Q(SASA): 0.6576
• 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/F	rs1477979232	None	0.863	N	0.367	0.297	0.806042141942	gnomAD-4.0.0	1.59192E-06	None	None	None	None	N	None	0	0	None	0	2.775E-05	None	0	0	0	0	0
V/G	rs762099144	-0.453	0.473	N	0.421	0.214	0.751175389254	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
V/G	rs762099144	-0.453	0.473	N	0.421	0.214	0.751175389254	gnomAD-4.0.0	3.1838E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.86599E-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	0.1155	likely_benign	0.1036	benign	-0.472	Destabilizing	0.27	N	0.191	neutral	N	0.501925774	None	None	N
V/C	0.6016	likely_pathogenic	0.6215	pathogenic	-0.859	Destabilizing	0.995	D	0.344	neutral	None	None	None	None	N
V/D	0.1621	likely_benign	0.1544	benign	-0.183	Destabilizing	0.642	D	0.421	neutral	D	0.524245273	None	None	N
V/E	0.1685	likely_benign	0.1577	benign	-0.271	Destabilizing	0.543	D	0.366	neutral	None	None	None	None	N
V/F	0.0984	likely_benign	0.0972	benign	-0.632	Destabilizing	0.863	D	0.367	neutral	N	0.490643534	None	None	N
V/G	0.1393	likely_benign	0.134	benign	-0.588	Destabilizing	0.473	N	0.421	neutral	N	0.506814305	None	None	N
V/H	0.3353	likely_benign	0.3189	benign	-0.046	Destabilizing	0.944	D	0.377	neutral	None	None	None	None	N
V/I	0.0759	likely_benign	0.0733	benign	-0.303	Destabilizing	0.27	N	0.269	neutral	N	0.480590496	None	None	N
V/K	0.2217	likely_benign	0.2023	benign	-0.457	Destabilizing	0.543	D	0.359	neutral	None	None	None	None	N
V/L	0.1258	likely_benign	0.1168	benign	-0.303	Destabilizing	0.002	N	0.12	neutral	N	0.494423798	None	None	N
V/M	0.1273	likely_benign	0.1143	benign	-0.602	Destabilizing	0.176	N	0.162	neutral	None	None	None	None	N
V/N	0.1486	likely_benign	0.1394	benign	-0.337	Destabilizing	0.704	D	0.394	neutral	None	None	None	None	N
V/P	0.2446	likely_benign	0.2285	benign	-0.329	Destabilizing	0.944	D	0.399	neutral	None	None	None	None	N
V/Q	0.2035	likely_benign	0.1868	benign	-0.497	Destabilizing	0.085	N	0.224	neutral	None	None	None	None	N
V/R	0.1814	likely_benign	0.1683	benign	-0.009	Destabilizing	0.704	D	0.416	neutral	None	None	None	None	N
V/S	0.1156	likely_benign	0.1073	benign	-0.707	Destabilizing	0.031	N	0.226	neutral	None	None	None	None	N
V/T	0.1198	likely_benign	0.107	benign	-0.689	Destabilizing	0.031	N	0.173	neutral	None	None	None	None	N
V/W	0.6105	likely_pathogenic	0.5983	pathogenic	-0.7	Destabilizing	0.995	D	0.4	neutral	None	None	None	None	N
V/Y	0.3393	likely_benign	0.3365	benign	-0.429	Destabilizing	0.981	D	0.362	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.