TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15661	47206;47207;47208	chr2:178618477;178618476;178618475	chr2:179483204;179483203;179483202
N2AB	14020	42283;42284;42285	chr2:178618477;178618476;178618475	chr2:179483204;179483203;179483202
N2A	13093	39502;39503;39504	chr2:178618477;178618476;178618475	chr2:179483204;179483203;179483202
N2B	6596	20011;20012;20013	chr2:178618477;178618476;178618475	chr2:179483204;179483203;179483202
Novex-1	6721	20386;20387;20388	chr2:178618477;178618476;178618475	chr2:179483204;179483203;179483202
Novex-2	6788	20587;20588;20589	chr2:178618477;178618476;178618475	chr2:179483204;179483203;179483202
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: Fn3-1
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.0775
• 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	rs774091228	-2.636	0.999	N	0.797	0.409	0.473143432122	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	6.48E-05	0	None	0	0	None	0	None	0	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	0.7264	likely_pathogenic	0.7944	pathogenic	-2.207	Highly Destabilizing	0.999	D	0.797	deleterious	N	0.473264555	None	None	N
V/C	0.9107	likely_pathogenic	0.9274	pathogenic	-1.841	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
V/D	0.9974	likely_pathogenic	0.9973	pathogenic	-3.173	Highly Destabilizing	1.0	D	0.919	deleterious	None	None	None	None	N
V/E	0.992	likely_pathogenic	0.9914	pathogenic	-2.917	Highly Destabilizing	1.0	D	0.915	deleterious	N	0.517132571	None	None	N
V/F	0.9564	likely_pathogenic	0.9647	pathogenic	-1.144	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
V/G	0.9313	likely_pathogenic	0.9435	pathogenic	-2.767	Highly Destabilizing	1.0	D	0.915	deleterious	D	0.560178877	None	None	N
V/H	0.9985	likely_pathogenic	0.9986	pathogenic	-2.587	Highly Destabilizing	1.0	D	0.935	deleterious	None	None	None	None	N
V/I	0.1321	likely_benign	0.1472	benign	-0.613	Destabilizing	0.997	D	0.679	prob.neutral	N	0.474787473	None	None	N
V/K	0.9964	likely_pathogenic	0.9957	pathogenic	-1.796	Destabilizing	1.0	D	0.917	deleterious	None	None	None	None	N
V/L	0.6903	likely_pathogenic	0.7739	pathogenic	-0.613	Destabilizing	0.997	D	0.786	deleterious	N	0.4622208	None	None	N
V/M	0.8371	likely_pathogenic	0.8745	pathogenic	-0.878	Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	N
V/N	0.9911	likely_pathogenic	0.9904	pathogenic	-2.256	Highly Destabilizing	1.0	D	0.937	deleterious	None	None	None	None	N
V/P	0.439	ambiguous	0.4872	ambiguous	-1.121	Destabilizing	1.0	D	0.916	deleterious	None	None	None	None	N
V/Q	0.9932	likely_pathogenic	0.9931	pathogenic	-2.023	Highly Destabilizing	1.0	D	0.937	deleterious	None	None	None	None	N
V/R	0.9923	likely_pathogenic	0.9912	pathogenic	-1.729	Destabilizing	1.0	D	0.94	deleterious	None	None	None	None	N
V/S	0.9481	likely_pathogenic	0.9557	pathogenic	-2.808	Highly Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
V/T	0.8693	likely_pathogenic	0.8904	pathogenic	-2.411	Highly Destabilizing	0.999	D	0.793	deleterious	None	None	None	None	N
V/W	0.9994	likely_pathogenic	0.9996	pathogenic	-1.754	Destabilizing	1.0	D	0.933	deleterious	None	None	None	None	N
V/Y	0.9973	likely_pathogenic	0.9977	pathogenic	-1.402	Destabilizing	1.0	D	0.867	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.