TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32554	97885;97886;97887	chr2:178541417;178541416;178541415	chr2:179406144;179406143;179406142
N2AB	30913	92962;92963;92964	chr2:178541417;178541416;178541415	chr2:179406144;179406143;179406142
N2A	29986	90181;90182;90183	chr2:178541417;178541416;178541415	chr2:179406144;179406143;179406142
N2B	23489	70690;70691;70692	chr2:178541417;178541416;178541415	chr2:179406144;179406143;179406142
Novex-1	23614	71065;71066;71067	chr2:178541417;178541416;178541415	chr2:179406144;179406143;179406142
Novex-2	23681	71266;71267;71268	chr2:178541417;178541416;178541415	chr2:179406144;179406143;179406142
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Fn3-125
• Domain position: 56
• Structural Position: 77
• Q(SASA): 0.0876
• 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/M	None	None	0.999	N	0.695	0.333	0.583991495718	gnomAD-4.0.0	1.59252E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86026E-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	0.6283	likely_pathogenic	0.6215	pathogenic	-1.696	Destabilizing	0.543	D	0.333	neutral	N	0.512342263	None	None	N
V/C	0.8922	likely_pathogenic	0.8842	pathogenic	-1.137	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
V/D	0.9759	likely_pathogenic	0.9693	pathogenic	-2.064	Highly Destabilizing	0.999	D	0.737	prob.delet.	None	None	None	None	N
V/E	0.9324	likely_pathogenic	0.9195	pathogenic	-1.844	Destabilizing	0.998	D	0.654	neutral	N	0.47249442	None	None	N
V/F	0.6953	likely_pathogenic	0.6665	pathogenic	-0.969	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
V/G	0.8009	likely_pathogenic	0.7848	pathogenic	-2.236	Highly Destabilizing	0.997	D	0.698	prob.neutral	N	0.492295065	None	None	N
V/H	0.9791	likely_pathogenic	0.9754	pathogenic	-2.084	Highly Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
V/I	0.0879	likely_benign	0.0857	benign	-0.202	Destabilizing	0.99	D	0.544	neutral	None	None	None	None	N
V/K	0.9574	likely_pathogenic	0.9502	pathogenic	-1.328	Destabilizing	0.999	D	0.664	neutral	None	None	None	None	N
V/L	0.3961	ambiguous	0.3863	ambiguous	-0.202	Destabilizing	0.973	D	0.549	neutral	N	0.472293837	None	None	N
V/M	0.3617	ambiguous	0.3639	ambiguous	-0.237	Destabilizing	0.999	D	0.695	prob.neutral	N	0.485878642	None	None	N
V/N	0.9098	likely_pathogenic	0.8999	pathogenic	-1.622	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
V/P	0.9805	likely_pathogenic	0.9747	pathogenic	-0.671	Destabilizing	0.999	D	0.699	prob.neutral	None	None	None	None	N
V/Q	0.9101	likely_pathogenic	0.9018	pathogenic	-1.437	Destabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	N
V/R	0.938	likely_pathogenic	0.9302	pathogenic	-1.278	Destabilizing	0.999	D	0.759	deleterious	None	None	None	None	N
V/S	0.7947	likely_pathogenic	0.7824	pathogenic	-2.252	Highly Destabilizing	0.995	D	0.667	neutral	None	None	None	None	N
V/T	0.6156	likely_pathogenic	0.6075	pathogenic	-1.882	Destabilizing	0.992	D	0.591	neutral	None	None	None	None	N
V/W	0.9926	likely_pathogenic	0.9907	pathogenic	-1.512	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
V/Y	0.9613	likely_pathogenic	0.9562	pathogenic	-1.056	Destabilizing	1.0	D	0.726	prob.delet.	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.