TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16826	50701;50702;50703	chr2:178611833;178611832;178611831	chr2:179476560;179476559;179476558
N2AB	15185	45778;45779;45780	chr2:178611833;178611832;178611831	chr2:179476560;179476559;179476558
N2A	14258	42997;42998;42999	chr2:178611833;178611832;178611831	chr2:179476560;179476559;179476558
N2B	7761	23506;23507;23508	chr2:178611833;178611832;178611831	chr2:179476560;179476559;179476558
Novex-1	7886	23881;23882;23883	chr2:178611833;178611832;178611831	chr2:179476560;179476559;179476558
Novex-2	7953	24082;24083;24084	chr2:178611833;178611832;178611831	chr2:179476560;179476559;179476558
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: Fn3-10
• Domain position: 76
• Structural Position: 108
• Q(SASA): 0.0729
• 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/L	None	None	0.997	D	0.697	0.575	0.733398536896	gnomAD-4.0.0	4.10712E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.39861E-06	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	0.9443	likely_pathogenic	0.9368	pathogenic	-2.403	Highly Destabilizing	0.999	D	0.679	prob.neutral	D	0.712658638	None	None	N
V/C	0.9842	likely_pathogenic	0.9801	pathogenic	-1.981	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
V/D	0.9992	likely_pathogenic	0.9992	pathogenic	-3.417	Highly Destabilizing	1.0	D	0.893	deleterious	D	0.787334041	None	None	N
V/E	0.9967	likely_pathogenic	0.9971	pathogenic	-3.099	Highly Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
V/F	0.976	likely_pathogenic	0.9699	pathogenic	-1.277	Destabilizing	1.0	D	0.843	deleterious	D	0.786292884	None	None	N
V/G	0.9586	likely_pathogenic	0.9595	pathogenic	-3.009	Highly Destabilizing	1.0	D	0.884	deleterious	D	0.787334041	None	None	N
V/H	0.9996	likely_pathogenic	0.9995	pathogenic	-2.875	Highly Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
V/I	0.2123	likely_benign	0.1996	benign	-0.633	Destabilizing	0.997	D	0.653	neutral	N	0.514449954	None	None	N
V/K	0.9981	likely_pathogenic	0.9983	pathogenic	-1.912	Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
V/L	0.8713	likely_pathogenic	0.8639	pathogenic	-0.633	Destabilizing	0.997	D	0.697	prob.neutral	D	0.694431663	None	None	N
V/M	0.9393	likely_pathogenic	0.9282	pathogenic	-1.026	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
V/N	0.9975	likely_pathogenic	0.9972	pathogenic	-2.587	Highly Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
V/P	0.998	likely_pathogenic	0.9979	pathogenic	-1.205	Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	N
V/Q	0.9972	likely_pathogenic	0.9972	pathogenic	-2.235	Highly Destabilizing	1.0	D	0.898	deleterious	None	None	None	None	N
V/R	0.9956	likely_pathogenic	0.9958	pathogenic	-1.996	Destabilizing	1.0	D	0.904	deleterious	None	None	None	None	N
V/S	0.9891	likely_pathogenic	0.9882	pathogenic	-3.099	Highly Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
V/T	0.9697	likely_pathogenic	0.9694	pathogenic	-2.624	Highly Destabilizing	0.999	D	0.701	prob.neutral	None	None	None	None	N
V/W	0.9997	likely_pathogenic	0.9997	pathogenic	-1.859	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
V/Y	0.9978	likely_pathogenic	0.9974	pathogenic	-1.557	Destabilizing	1.0	D	0.838	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.