TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17519	52780;52781;52782	chr2:178608328;178608327;178608326	chr2:179473055;179473054;179473053
N2AB	15878	47857;47858;47859	chr2:178608328;178608327;178608326	chr2:179473055;179473054;179473053
N2A	14951	45076;45077;45078	chr2:178608328;178608327;178608326	chr2:179473055;179473054;179473053
N2B	8454	25585;25586;25587	chr2:178608328;178608327;178608326	chr2:179473055;179473054;179473053
Novex-1	8579	25960;25961;25962	chr2:178608328;178608327;178608326	chr2:179473055;179473054;179473053
Novex-2	8646	26161;26162;26163	chr2:178608328;178608327;178608326	chr2:179473055;179473054;179473053
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: Fn3-15
• Domain position: 50
• Structural Position: 68
• Q(SASA): 0.2993
• 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/F	None	None	1.0	N	0.828	0.472	0.603745951297	gnomAD-4.0.0	1.59428E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86254E-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	0.301	likely_benign	0.3313	benign	-1.259	Destabilizing	0.999	D	0.549	neutral	N	0.479539198	None	None	N
V/C	0.7552	likely_pathogenic	0.7553	pathogenic	-0.913	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
V/D	0.8812	likely_pathogenic	0.9214	pathogenic	-0.849	Destabilizing	1.0	D	0.856	deleterious	N	0.502007887	None	None	N
V/E	0.7039	likely_pathogenic	0.7697	pathogenic	-0.832	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
V/F	0.395	ambiguous	0.484	ambiguous	-0.89	Destabilizing	1.0	D	0.828	deleterious	N	0.476595797	None	None	N
V/G	0.4975	ambiguous	0.5734	pathogenic	-1.586	Destabilizing	1.0	D	0.815	deleterious	N	0.507034317	None	None	N
V/H	0.9051	likely_pathogenic	0.9232	pathogenic	-1.07	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
V/I	0.0958	likely_benign	0.1027	benign	-0.463	Destabilizing	0.997	D	0.471	neutral	N	0.479923201	None	None	N
V/K	0.8631	likely_pathogenic	0.8859	pathogenic	-1.082	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
V/L	0.4199	ambiguous	0.4927	ambiguous	-0.463	Destabilizing	0.997	D	0.529	neutral	N	0.486849173	None	None	N
V/M	0.3271	likely_benign	0.3877	ambiguous	-0.419	Destabilizing	1.0	D	0.682	prob.neutral	None	None	None	None	N
V/N	0.7309	likely_pathogenic	0.8051	pathogenic	-0.945	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
V/P	0.9312	likely_pathogenic	0.9424	pathogenic	-0.692	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
V/Q	0.7118	likely_pathogenic	0.7751	pathogenic	-1.045	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
V/R	0.8313	likely_pathogenic	0.8636	pathogenic	-0.63	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
V/S	0.5347	ambiguous	0.6188	pathogenic	-1.498	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
V/T	0.4783	ambiguous	0.5441	ambiguous	-1.358	Destabilizing	0.999	D	0.558	neutral	None	None	None	None	N
V/W	0.9603	likely_pathogenic	0.9674	pathogenic	-1.094	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
V/Y	0.8311	likely_pathogenic	0.8583	pathogenic	-0.778	Destabilizing	1.0	D	0.831	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.