TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25081	75466;75467;75468	chr2:178570891;178570890;178570889	chr2:179435618;179435617;179435616
N2AB	23440	70543;70544;70545	chr2:178570891;178570890;178570889	chr2:179435618;179435617;179435616
N2A	22513	67762;67763;67764	chr2:178570891;178570890;178570889	chr2:179435618;179435617;179435616
N2B	16016	48271;48272;48273	chr2:178570891;178570890;178570889	chr2:179435618;179435617;179435616
Novex-1	16141	48646;48647;48648	chr2:178570891;178570890;178570889	chr2:179435618;179435617;179435616
Novex-2	16208	48847;48848;48849	chr2:178570891;178570890;178570889	chr2:179435618;179435617;179435616
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: Fn3-70
• Domain position: 76
• Structural Position: 108
• Q(SASA): 0.0968
• 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	None	None	0.067	D	0.327	0.248	0.326881540566	gnomAD-4.0.0	3.18346E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71873E-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	0.7689	likely_pathogenic	0.7652	pathogenic	-2.622	Highly Destabilizing	0.958	D	0.693	prob.neutral	D	0.54606066	None	None	N
V/C	0.9495	likely_pathogenic	0.9493	pathogenic	-1.986	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
V/D	0.9984	likely_pathogenic	0.9979	pathogenic	-3.272	Highly Destabilizing	0.998	D	0.901	deleterious	D	0.647360344	None	None	N
V/E	0.9949	likely_pathogenic	0.9937	pathogenic	-2.972	Highly Destabilizing	0.998	D	0.881	deleterious	None	None	None	None	N
V/F	0.9518	likely_pathogenic	0.9396	pathogenic	-1.263	Destabilizing	0.988	D	0.847	deleterious	D	0.5508336	None	None	N
V/G	0.9416	likely_pathogenic	0.9285	pathogenic	-3.168	Highly Destabilizing	0.994	D	0.895	deleterious	D	0.647360344	None	None	N
V/H	0.9989	likely_pathogenic	0.9986	pathogenic	-2.835	Highly Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	N
V/I	0.0996	likely_benign	0.0966	benign	-1.013	Destabilizing	0.067	N	0.327	neutral	D	0.525848357	None	None	N
V/K	0.9976	likely_pathogenic	0.997	pathogenic	-1.912	Destabilizing	0.995	D	0.883	deleterious	None	None	None	None	N
V/L	0.7764	likely_pathogenic	0.7374	pathogenic	-1.013	Destabilizing	0.618	D	0.652	neutral	N	0.517646375	None	None	N
V/M	0.8049	likely_pathogenic	0.7667	pathogenic	-1.423	Destabilizing	0.991	D	0.819	deleterious	None	None	None	None	N
V/N	0.9913	likely_pathogenic	0.9888	pathogenic	-2.526	Highly Destabilizing	0.998	D	0.91	deleterious	None	None	None	None	N
V/P	0.996	likely_pathogenic	0.995	pathogenic	-1.536	Destabilizing	0.998	D	0.897	deleterious	None	None	None	None	N
V/Q	0.9952	likely_pathogenic	0.994	pathogenic	-2.177	Highly Destabilizing	0.998	D	0.905	deleterious	None	None	None	None	N
V/R	0.9949	likely_pathogenic	0.9939	pathogenic	-1.972	Destabilizing	0.998	D	0.912	deleterious	None	None	None	None	N
V/S	0.947	likely_pathogenic	0.9399	pathogenic	-2.997	Highly Destabilizing	0.995	D	0.887	deleterious	None	None	None	None	N
V/T	0.8984	likely_pathogenic	0.8918	pathogenic	-2.56	Highly Destabilizing	0.968	D	0.76	deleterious	None	None	None	None	N
V/W	0.9994	likely_pathogenic	0.9993	pathogenic	-1.721	Destabilizing	1.0	D	0.872	deleterious	None	None	None	None	N
V/Y	0.996	likely_pathogenic	0.9949	pathogenic	-1.567	Destabilizing	0.995	D	0.855	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.