TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7148	21667;21668;21669	chr2:178723658;178723657;178723656	chr2:179588385;179588384;179588383
N2AB	6831	20716;20717;20718	chr2:178723658;178723657;178723656	chr2:179588385;179588384;179588383
N2A	5904	17935;17936;17937	chr2:178723658;178723657;178723656	chr2:179588385;179588384;179588383
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: GTA
• RefSeq wild type template codon: CAT
• Domain: Ig-56
• Domain position: 12
• Structural Position: 16
• Q(SASA): 0.104
• 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/G	None	None	None	D	0.367	0.293	0.764626318615	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
V/I	rs778943017	-0.207	None	N	0.159	0.205	0.258779203287	gnomAD-2.1.1	1.25E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.17E-06	3.46141E-04
V/I	rs778943017	-0.207	None	N	0.159	0.205	0.258779203287	gnomAD-4.0.0	8.06975E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	2.44858E-04	2.89051E-06	0	9.18892E-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	0.1628	likely_benign	0.17	benign	-1.982	Destabilizing	None	N	0.157	neutral	N	0.493389222	None	None	N
V/C	0.7374	likely_pathogenic	0.7506	pathogenic	-1.37	Destabilizing	0.935	D	0.571	neutral	None	None	None	None	N
V/D	0.4077	ambiguous	0.4501	ambiguous	-2.562	Highly Destabilizing	0.555	D	0.649	neutral	None	None	None	None	N
V/E	0.3783	ambiguous	0.3978	ambiguous	-2.361	Highly Destabilizing	0.317	N	0.62	neutral	D	0.550981276	None	None	N
V/F	0.1809	likely_benign	0.2037	benign	-1.181	Destabilizing	0.38	N	0.631	neutral	None	None	None	None	N
V/G	0.2142	likely_benign	0.2365	benign	-2.486	Highly Destabilizing	None	N	0.367	neutral	D	0.543979837	None	None	N
V/H	0.6806	likely_pathogenic	0.7117	pathogenic	-2.177	Highly Destabilizing	0.935	D	0.59	neutral	None	None	None	None	N
V/I	0.0882	likely_benign	0.0909	benign	-0.589	Destabilizing	None	N	0.159	neutral	N	0.497043224	None	None	N
V/K	0.5345	ambiguous	0.5468	ambiguous	-1.914	Destabilizing	0.38	N	0.625	neutral	None	None	None	None	N
V/L	0.2174	likely_benign	0.218	benign	-0.589	Destabilizing	0.009	N	0.389	neutral	N	0.506299616	None	None	N
V/M	0.1656	likely_benign	0.1713	benign	-0.48	Destabilizing	0.38	N	0.543	neutral	None	None	None	None	N
V/N	0.3456	ambiguous	0.3859	ambiguous	-2.175	Highly Destabilizing	0.555	D	0.64	neutral	None	None	None	None	N
V/P	0.8342	likely_pathogenic	0.8732	pathogenic	-1.026	Destabilizing	0.555	D	0.617	neutral	None	None	None	None	N
V/Q	0.4767	ambiguous	0.4983	ambiguous	-2.056	Highly Destabilizing	0.555	D	0.619	neutral	None	None	None	None	N
V/R	0.4817	ambiguous	0.4907	ambiguous	-1.627	Destabilizing	0.555	D	0.652	neutral	None	None	None	None	N
V/S	0.23	likely_benign	0.2545	benign	-2.743	Highly Destabilizing	0.081	N	0.541	neutral	None	None	None	None	N
V/T	0.1981	likely_benign	0.1991	benign	-2.41	Highly Destabilizing	0.149	N	0.501	neutral	None	None	None	None	N
V/W	0.8415	likely_pathogenic	0.8669	pathogenic	-1.707	Destabilizing	0.935	D	0.6	neutral	None	None	None	None	N
V/Y	0.5337	ambiguous	0.5716	pathogenic	-1.305	Destabilizing	0.555	D	0.643	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.