TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26999	81220;81221;81222	chr2:178565137;178565136;178565135	chr2:179429864;179429863;179429862
N2AB	25358	76297;76298;76299	chr2:178565137;178565136;178565135	chr2:179429864;179429863;179429862
N2A	24431	73516;73517;73518	chr2:178565137;178565136;178565135	chr2:179429864;179429863;179429862
N2B	17934	54025;54026;54027	chr2:178565137;178565136;178565135	chr2:179429864;179429863;179429862
Novex-1	18059	54400;54401;54402	chr2:178565137;178565136;178565135	chr2:179429864;179429863;179429862
Novex-2	18126	54601;54602;54603	chr2:178565137;178565136;178565135	chr2:179429864;179429863;179429862
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-84
• Domain position: 28
• Structural Position: 29
• Q(SASA): 0.6743
• Predicted PPI site: I

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
Y/C	rs1252117916	None	0.999	N	0.656	0.543	0.602722737475	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
Y/C	rs1252117916	None	0.999	N	0.656	0.543	0.602722737475	gnomAD-4.0.0	4.33876E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.93414E-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
Y/A	0.6974	likely_pathogenic	0.6997	pathogenic	-0.809	Destabilizing	0.916	D	0.497	neutral	None	None	None	None	I
Y/C	0.3036	likely_benign	0.2789	benign	-0.007	Destabilizing	0.999	D	0.656	neutral	N	0.507369349	None	None	I
Y/D	0.3734	ambiguous	0.4124	ambiguous	1.041	Stabilizing	0.025	N	0.489	neutral	N	0.427717938	None	None	I
Y/E	0.7873	likely_pathogenic	0.798	pathogenic	1.028	Stabilizing	0.845	D	0.495	neutral	None	None	None	None	I
Y/F	0.1155	likely_benign	0.1102	benign	-0.376	Destabilizing	0.981	D	0.544	neutral	N	0.493695	None	None	I
Y/G	0.6365	likely_pathogenic	0.6562	pathogenic	-0.998	Destabilizing	0.975	D	0.521	neutral	None	None	None	None	I
Y/H	0.3743	ambiguous	0.3653	ambiguous	0.18	Stabilizing	0.994	D	0.579	neutral	N	0.494676435	None	None	I
Y/I	0.6753	likely_pathogenic	0.6753	pathogenic	-0.331	Destabilizing	0.987	D	0.575	neutral	None	None	None	None	I
Y/K	0.8445	likely_pathogenic	0.8574	pathogenic	0.14	Stabilizing	0.975	D	0.605	neutral	None	None	None	None	I
Y/L	0.6062	likely_pathogenic	0.5941	pathogenic	-0.331	Destabilizing	0.957	D	0.564	neutral	None	None	None	None	I
Y/M	0.7311	likely_pathogenic	0.7211	pathogenic	-0.142	Destabilizing	0.999	D	0.567	neutral	None	None	None	None	I
Y/N	0.1981	likely_benign	0.2105	benign	-0.054	Destabilizing	0.935	D	0.609	neutral	N	0.509259099	None	None	I
Y/P	0.9695	likely_pathogenic	0.9668	pathogenic	-0.471	Destabilizing	0.987	D	0.66	neutral	None	None	None	None	I
Y/Q	0.7573	likely_pathogenic	0.7502	pathogenic	-0.015	Destabilizing	0.987	D	0.571	neutral	None	None	None	None	I
Y/R	0.7433	likely_pathogenic	0.7507	pathogenic	0.434	Stabilizing	0.987	D	0.613	neutral	None	None	None	None	I
Y/S	0.319	likely_benign	0.3377	benign	-0.557	Destabilizing	0.967	D	0.469	neutral	N	0.472087577	None	None	I
Y/T	0.5968	likely_pathogenic	0.6154	pathogenic	-0.481	Destabilizing	0.975	D	0.566	neutral	None	None	None	None	I
Y/V	0.5321	ambiguous	0.5288	ambiguous	-0.471	Destabilizing	0.987	D	0.515	neutral	None	None	None	None	I
Y/W	0.5553	ambiguous	0.5537	ambiguous	-0.436	Destabilizing	0.999	D	0.559	neutral	None	None	None	None	I

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.