TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16563	49912;49913;49914	chr2:178613034;178613033;178613032	chr2:179477761;179477760;179477759
N2AB	14922	44989;44990;44991	chr2:178613034;178613033;178613032	chr2:179477761;179477760;179477759
N2A	13995	42208;42209;42210	chr2:178613034;178613033;178613032	chr2:179477761;179477760;179477759
N2B	7498	22717;22718;22719	chr2:178613034;178613033;178613032	chr2:179477761;179477760;179477759
Novex-1	7623	23092;23093;23094	chr2:178613034;178613033;178613032	chr2:179477761;179477760;179477759
Novex-2	7690	23293;23294;23295	chr2:178613034;178613033;178613032	chr2:179477761;179477760;179477759
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Fn3-8
• Domain position: 13
• Structural Position: 15
• Q(SASA): 0.4246
• 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	rs2056630981	None	0.002	N	0.187	0.18	0.124217242631	gnomAD-4.0.0	1.59351E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.0303E-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	0.1821	likely_benign	0.1721	benign	-1.345	Destabilizing	0.334	N	0.416	neutral	N	0.482765009	None	None	N
V/C	0.7487	likely_pathogenic	0.6931	pathogenic	-1.276	Destabilizing	0.982	D	0.707	prob.neutral	None	None	None	None	N
V/D	0.67	likely_pathogenic	0.7057	pathogenic	-1.193	Destabilizing	0.826	D	0.805	deleterious	None	None	None	None	N
V/E	0.5571	ambiguous	0.5875	pathogenic	-1.218	Destabilizing	0.781	D	0.761	deleterious	D	0.662165364	None	None	N
V/F	0.2323	likely_benign	0.2189	benign	-1.317	Destabilizing	0.7	D	0.733	prob.delet.	None	None	None	None	N
V/G	0.3909	ambiguous	0.3971	ambiguous	-1.613	Destabilizing	0.781	D	0.797	deleterious	D	0.642873496	None	None	N
V/H	0.7378	likely_pathogenic	0.7189	pathogenic	-1.218	Destabilizing	0.982	D	0.798	deleterious	None	None	None	None	N
V/I	0.0629	likely_benign	0.0576	benign	-0.723	Destabilizing	0.002	N	0.187	neutral	N	0.464990547	None	None	N
V/K	0.5807	likely_pathogenic	0.6101	pathogenic	-0.961	Destabilizing	0.826	D	0.763	deleterious	None	None	None	None	N
V/L	0.2358	likely_benign	0.1899	benign	-0.723	Destabilizing	0.034	N	0.314	neutral	N	0.47106358	None	None	N
V/M	0.1853	likely_benign	0.1571	benign	-0.69	Destabilizing	0.7	D	0.642	neutral	None	None	None	None	N
V/N	0.4679	ambiguous	0.4492	ambiguous	-0.795	Destabilizing	0.935	D	0.798	deleterious	None	None	None	None	N
V/P	0.5804	likely_pathogenic	0.5973	pathogenic	-0.897	Destabilizing	0.935	D	0.781	deleterious	None	None	None	None	N
V/Q	0.562	ambiguous	0.5574	ambiguous	-1.023	Destabilizing	0.935	D	0.772	deleterious	None	None	None	None	N
V/R	0.4684	ambiguous	0.519	ambiguous	-0.524	Destabilizing	0.826	D	0.797	deleterious	None	None	None	None	N
V/S	0.2958	likely_benign	0.278	benign	-1.324	Destabilizing	0.826	D	0.763	deleterious	None	None	None	None	N
V/T	0.1486	likely_benign	0.1262	benign	-1.238	Destabilizing	0.399	N	0.525	neutral	None	None	None	None	N
V/W	0.8357	likely_pathogenic	0.8266	pathogenic	-1.429	Destabilizing	0.982	D	0.8	deleterious	None	None	None	None	N
V/Y	0.6586	likely_pathogenic	0.6356	pathogenic	-1.097	Destabilizing	0.826	D	0.751	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.