TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8957	27094;27095;27096	chr2:178713265;178713264;178713263	chr2:179577992;179577991;179577990
N2AB	8640	26143;26144;26145	chr2:178713265;178713264;178713263	chr2:179577992;179577991;179577990
N2A	7713	23362;23363;23364	chr2:178713265;178713264;178713263	chr2:179577992;179577991;179577990
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: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-75
• Domain position: 32
• Structural Position: 46
• Q(SASA): 0.3239
• 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	rs1008014872	None	0.008	N	0.22	0.114	0.376921832658	gnomAD-3.1.2	4.6E-05	None	None	None	None	N	None	1.69033E-04	0	0	0	0	None	0	0	0	0	0
V/I	rs1008014872	None	0.008	N	0.22	0.114	0.376921832658	gnomAD-4.0.0	5.58425E-06	None	None	None	None	N	None	1.20218E-04	0	None	0	0	None	0	0	0	0	0
V/L	None	None	0.156	D	0.584	0.445	0.400899426204	gnomAD-4.0.0	6.85124E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00276E-07	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	0.444	ambiguous	0.5137	ambiguous	-1.439	Destabilizing	0.517	D	0.654	neutral	D	0.576175082	None	None	N
V/C	0.8889	likely_pathogenic	0.9068	pathogenic	-1.013	Destabilizing	0.996	D	0.721	prob.delet.	None	None	None	None	N
V/D	0.9478	likely_pathogenic	0.964	pathogenic	-0.973	Destabilizing	0.949	D	0.855	deleterious	D	0.630581973	None	None	N
V/E	0.894	likely_pathogenic	0.9248	pathogenic	-0.932	Destabilizing	0.961	D	0.837	deleterious	None	None	None	None	N
V/F	0.3444	ambiguous	0.3584	ambiguous	-1.037	Destabilizing	0.901	D	0.759	deleterious	D	0.538362604	None	None	N
V/G	0.6837	likely_pathogenic	0.7361	pathogenic	-1.808	Destabilizing	0.949	D	0.827	deleterious	D	0.630581973	None	None	N
V/H	0.948	likely_pathogenic	0.9635	pathogenic	-1.388	Destabilizing	0.996	D	0.833	deleterious	None	None	None	None	N
V/I	0.0787	likely_benign	0.0771	benign	-0.512	Destabilizing	0.008	N	0.22	neutral	N	0.458068714	None	None	N
V/K	0.9047	likely_pathogenic	0.9327	pathogenic	-1.085	Destabilizing	0.961	D	0.839	deleterious	None	None	None	None	N
V/L	0.3181	likely_benign	0.3389	benign	-0.512	Destabilizing	0.156	N	0.584	neutral	D	0.538575127	None	None	N
V/M	0.2623	likely_benign	0.3078	benign	-0.449	Destabilizing	0.923	D	0.655	neutral	None	None	None	None	N
V/N	0.8661	likely_pathogenic	0.9012	pathogenic	-0.918	Destabilizing	0.961	D	0.851	deleterious	None	None	None	None	N
V/P	0.8984	likely_pathogenic	0.931	pathogenic	-0.785	Destabilizing	0.987	D	0.841	deleterious	None	None	None	None	N
V/Q	0.8824	likely_pathogenic	0.9068	pathogenic	-0.995	Destabilizing	0.987	D	0.845	deleterious	None	None	None	None	N
V/R	0.8752	likely_pathogenic	0.8953	pathogenic	-0.718	Destabilizing	0.961	D	0.839	deleterious	None	None	None	None	N
V/S	0.6849	likely_pathogenic	0.7408	pathogenic	-1.534	Destabilizing	0.858	D	0.819	deleterious	None	None	None	None	N
V/T	0.5058	ambiguous	0.5896	pathogenic	-1.361	Destabilizing	0.096	N	0.413	neutral	None	None	None	None	N
V/W	0.9561	likely_pathogenic	0.9674	pathogenic	-1.26	Destabilizing	0.996	D	0.822	deleterious	None	None	None	None	N
V/Y	0.8485	likely_pathogenic	0.8725	pathogenic	-0.933	Destabilizing	0.961	D	0.737	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.