TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32929	99010;99011;99012	chr2:178539150;178539149;178539148	chr2:179403877;179403876;179403875
N2AB	31288	94087;94088;94089	chr2:178539150;178539149;178539148	chr2:179403877;179403876;179403875
N2A	30361	91306;91307;91308	chr2:178539150;178539149;178539148	chr2:179403877;179403876;179403875
N2B	23864	71815;71816;71817	chr2:178539150;178539149;178539148	chr2:179403877;179403876;179403875
Novex-1	23989	72190;72191;72192	chr2:178539150;178539149;178539148	chr2:179403877;179403876;179403875
Novex-2	24056	72391;72392;72393	chr2:178539150;178539149;178539148	chr2:179403877;179403876;179403875
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: Fn3-128
• Domain position: 34
• Structural Position: 35
• Q(SASA): 0.1829
• 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/A	None	None	0.998	N	0.63	0.408	0.62434799699	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	rs2154139645	None	0.767	N	0.363	0.237	0.411133732114	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

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	0.9457	likely_pathogenic	0.9377	pathogenic	-1.907	Destabilizing	0.998	D	0.63	neutral	N	0.482880129	None	None	N
V/C	0.9776	likely_pathogenic	0.9626	pathogenic	-1.357	Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
V/D	0.9926	likely_pathogenic	0.9883	pathogenic	-2.162	Highly Destabilizing	1.0	D	0.915	deleterious	N	0.520079099	None	None	N
V/E	0.9791	likely_pathogenic	0.9727	pathogenic	-2.101	Highly Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
V/F	0.8993	likely_pathogenic	0.8916	pathogenic	-1.434	Destabilizing	0.999	D	0.897	deleterious	N	0.503729407	None	None	N
V/G	0.9527	likely_pathogenic	0.9383	pathogenic	-2.302	Highly Destabilizing	1.0	D	0.898	deleterious	N	0.506771282	None	None	N
V/H	0.9956	likely_pathogenic	0.9918	pathogenic	-1.909	Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
V/I	0.0818	likely_benign	0.0802	benign	-0.878	Destabilizing	0.767	D	0.363	neutral	N	0.365325472	None	None	N
V/K	0.99	likely_pathogenic	0.9875	pathogenic	-1.592	Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
V/L	0.666	likely_pathogenic	0.6184	pathogenic	-0.878	Destabilizing	0.981	D	0.629	neutral	N	0.470476998	None	None	N
V/M	0.7411	likely_pathogenic	0.6959	pathogenic	-0.637	Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	N
V/N	0.9611	likely_pathogenic	0.9091	pathogenic	-1.518	Destabilizing	1.0	D	0.917	deleterious	None	None	None	None	N
V/P	0.932	likely_pathogenic	0.9379	pathogenic	-1.189	Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	N
V/Q	0.986	likely_pathogenic	0.98	pathogenic	-1.628	Destabilizing	1.0	D	0.908	deleterious	None	None	None	None	N
V/R	0.9858	likely_pathogenic	0.982	pathogenic	-1.098	Destabilizing	1.0	D	0.914	deleterious	None	None	None	None	N
V/S	0.9682	likely_pathogenic	0.9497	pathogenic	-2.071	Highly Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
V/T	0.9245	likely_pathogenic	0.907	pathogenic	-1.893	Destabilizing	0.998	D	0.73	prob.delet.	None	None	None	None	N
V/W	0.9976	likely_pathogenic	0.9957	pathogenic	-1.746	Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
V/Y	0.9877	likely_pathogenic	0.9803	pathogenic	-1.446	Destabilizing	1.0	D	0.896	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.