TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7885	23878;23879;23880	chr2:178719989;178719988;178719987	chr2:179584716;179584715;179584714
N2AB	7568	22927;22928;22929	chr2:178719989;178719988;178719987	chr2:179584716;179584715;179584714
N2A	6641	20146;20147;20148	chr2:178719989;178719988;178719987	chr2:179584716;179584715;179584714
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-63
• Domain position: 91
• Structural Position: 178
• Q(SASA): 0.2832
• 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	rs2078098721	None	0.973	D	0.691	0.768	0.83395928633	gnomAD-4.0.0	2.06364E-06	None	None	None	None	N	None	0	0	None	7.78938E-05	0	None	0	0	0	0	1.66689E-05
V/L	rs1438134317	-0.709	0.535	D	0.705	0.528	0.729328342088	gnomAD-2.1.1	4.16E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.43E-05	None	0	0	0
V/L	rs1438134317	-0.709	0.535	D	0.705	0.528	0.729328342088	gnomAD-4.0.0	3.22379E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.92184E-05	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	0.7283	likely_pathogenic	0.6672	pathogenic	-1.829	Destabilizing	0.973	D	0.691	prob.neutral	D	0.618982665	None	None	N
V/C	0.9607	likely_pathogenic	0.9417	pathogenic	-1.873	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
V/D	0.9838	likely_pathogenic	0.9791	pathogenic	-2.185	Highly Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
V/E	0.958	likely_pathogenic	0.9486	pathogenic	-2.126	Highly Destabilizing	0.997	D	0.797	deleterious	D	0.635607438	None	None	N
V/F	0.681	likely_pathogenic	0.616	pathogenic	-1.431	Destabilizing	0.997	D	0.809	deleterious	None	None	None	None	N
V/G	0.8711	likely_pathogenic	0.8436	pathogenic	-2.178	Highly Destabilizing	1.0	D	0.785	deleterious	D	0.635607438	None	None	N
V/H	0.9886	likely_pathogenic	0.9839	pathogenic	-1.597	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
V/I	0.0941	likely_benign	0.0845	benign	-0.934	Destabilizing	0.017	N	0.553	neutral	D	0.533377336	None	None	N
V/K	0.9801	likely_pathogenic	0.9755	pathogenic	-1.465	Destabilizing	0.997	D	0.794	deleterious	None	None	None	None	N
V/L	0.4996	ambiguous	0.4011	ambiguous	-0.934	Destabilizing	0.535	D	0.705	prob.neutral	D	0.600713096	None	None	N
V/M	0.4601	ambiguous	0.3978	ambiguous	-1.05	Destabilizing	0.995	D	0.833	deleterious	None	None	None	None	N
V/N	0.9415	likely_pathogenic	0.9174	pathogenic	-1.513	Destabilizing	0.993	D	0.814	deleterious	None	None	None	None	N
V/P	0.9622	likely_pathogenic	0.9383	pathogenic	-1.203	Destabilizing	0.993	D	0.808	deleterious	None	None	None	None	N
V/Q	0.9627	likely_pathogenic	0.9539	pathogenic	-1.666	Destabilizing	0.998	D	0.823	deleterious	None	None	None	None	N
V/R	0.9668	likely_pathogenic	0.9604	pathogenic	-1.016	Destabilizing	0.999	D	0.815	deleterious	None	None	None	None	N
V/S	0.8567	likely_pathogenic	0.8153	pathogenic	-2.099	Highly Destabilizing	0.997	D	0.786	deleterious	None	None	None	None	N
V/T	0.7555	likely_pathogenic	0.6896	pathogenic	-1.925	Destabilizing	0.95	D	0.772	deleterious	None	None	None	None	N
V/W	0.994	likely_pathogenic	0.9905	pathogenic	-1.618	Destabilizing	1.0	D	0.752	deleterious	None	None	None	None	N
V/Y	0.9698	likely_pathogenic	0.9574	pathogenic	-1.307	Destabilizing	0.999	D	0.813	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.