TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8026	24301;24302;24303	chr2:178719314;178719313;178719312	chr2:179584041;179584040;179584039
N2AB	7709	23350;23351;23352	chr2:178719314;178719313;178719312	chr2:179584041;179584040;179584039
N2A	6782	20569;20570;20571	chr2:178719314;178719313;178719312	chr2:179584041;179584040;179584039
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-65
• Domain position: 42
• Structural Position: 59
• Q(SASA): 0.612
• 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/D	None	None	0.055	N	0.411	0.207	0.650414729863	gnomAD-4.0.0	1.3684E-06	None	None	None	None	N	None	0	0	None	0	2.51915E-05	None	0	0	0	1.15931E-05	0
V/G	None	None	0.055	N	0.415	0.205	0.667366933581	gnomAD-4.0.0	6.84201E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99478E-07	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	0.0932	likely_benign	0.0972	benign	-0.358	Destabilizing	0.012	N	0.213	neutral	N	0.441050673	None	None	N
V/C	0.4424	ambiguous	0.4739	ambiguous	-0.804	Destabilizing	0.864	D	0.333	neutral	None	None	None	None	N
V/D	0.1506	likely_benign	0.1643	benign	-0.262	Destabilizing	0.055	N	0.411	neutral	N	0.46633312	None	None	N
V/E	0.1443	likely_benign	0.1637	benign	-0.377	Destabilizing	0.038	N	0.395	neutral	None	None	None	None	N
V/F	0.0799	likely_benign	0.0821	benign	-0.717	Destabilizing	None	N	0.187	neutral	N	0.496829385	None	None	N
V/G	0.1076	likely_benign	0.1176	benign	-0.419	Destabilizing	0.055	N	0.415	neutral	N	0.472605731	None	None	N
V/H	0.2166	likely_benign	0.2439	benign	-0.034	Destabilizing	0.001	N	0.321	neutral	None	None	None	None	N
V/I	0.0686	likely_benign	0.0668	benign	-0.339	Destabilizing	None	N	0.198	neutral	N	0.466853195	None	None	N
V/K	0.1383	likely_benign	0.1574	benign	-0.379	Destabilizing	0.038	N	0.373	neutral	None	None	None	None	N
V/L	0.0886	likely_benign	0.0959	benign	-0.339	Destabilizing	0.004	N	0.201	neutral	N	0.453481253	None	None	N
V/M	0.0965	likely_benign	0.1062	benign	-0.565	Destabilizing	0.214	N	0.302	neutral	None	None	None	None	N
V/N	0.1146	likely_benign	0.1255	benign	-0.19	Destabilizing	0.072	N	0.39	neutral	None	None	None	None	N
V/P	0.1682	likely_benign	0.1882	benign	-0.317	Destabilizing	0.356	N	0.372	neutral	None	None	None	None	N
V/Q	0.1422	likely_benign	0.1621	benign	-0.388	Destabilizing	0.007	N	0.267	neutral	None	None	None	None	N
V/R	0.1174	likely_benign	0.1254	benign	0.051	Stabilizing	0.214	N	0.401	neutral	None	None	None	None	N
V/S	0.0907	likely_benign	0.0979	benign	-0.51	Destabilizing	0.003	N	0.283	neutral	None	None	None	None	N
V/T	0.0974	likely_benign	0.1034	benign	-0.531	Destabilizing	0.038	N	0.192	neutral	None	None	None	None	N
V/W	0.4609	ambiguous	0.4847	ambiguous	-0.773	Destabilizing	0.864	D	0.363	neutral	None	None	None	None	N
V/Y	0.2451	likely_benign	0.2545	benign	-0.502	Destabilizing	0.038	N	0.38	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.