TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34338	103237;103238;103239	chr2:178533603;178533602;178533601	chr2:179398330;179398329;179398328
N2AB	32697	98314;98315;98316	chr2:178533603;178533602;178533601	chr2:179398330;179398329;179398328
N2A	31770	95533;95534;95535	chr2:178533603;178533602;178533601	chr2:179398330;179398329;179398328
N2B	25273	76042;76043;76044	chr2:178533603;178533602;178533601	chr2:179398330;179398329;179398328
Novex-1	25398	76417;76418;76419	chr2:178533603;178533602;178533601	chr2:179398330;179398329;179398328
Novex-2	25465	76618;76619;76620	chr2:178533603;178533602;178533601	chr2:179398330;179398329;179398328
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-161
• Domain position: 81
• Structural Position: 162
• Q(SASA): 0.8887
• 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
K/Q	None	None	0.994	N	0.587	0.427	0.377799810692	gnomAD-4.0.0	1.59099E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85767E-06	0	0
K/T	None	None	0.997	N	0.519	0.405	0.440498838766	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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
K/A	0.5877	likely_pathogenic	0.5933	pathogenic	-0.139	Destabilizing	0.983	D	0.519	neutral	None	None	None	None	I
K/C	0.8873	likely_pathogenic	0.9101	pathogenic	-0.482	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	I
K/D	0.8239	likely_pathogenic	0.83	pathogenic	-0.221	Destabilizing	0.998	D	0.547	neutral	None	None	None	None	I
K/E	0.4302	ambiguous	0.4481	ambiguous	-0.194	Destabilizing	0.978	D	0.523	neutral	N	0.471392223	None	None	I
K/F	0.954	likely_pathogenic	0.9628	pathogenic	-0.362	Destabilizing	1.0	D	0.627	neutral	None	None	None	None	I
K/G	0.7897	likely_pathogenic	0.8088	pathogenic	-0.327	Destabilizing	0.998	D	0.464	neutral	None	None	None	None	I
K/H	0.5927	likely_pathogenic	0.6274	pathogenic	-0.487	Destabilizing	1.0	D	0.554	neutral	None	None	None	None	I
K/I	0.5695	likely_pathogenic	0.6211	pathogenic	0.285	Stabilizing	0.999	D	0.634	neutral	N	0.499736404	None	None	I
K/L	0.6477	likely_pathogenic	0.6793	pathogenic	0.285	Stabilizing	0.995	D	0.464	neutral	None	None	None	None	I
K/M	0.4994	ambiguous	0.5643	pathogenic	-0.165	Destabilizing	1.0	D	0.562	neutral	None	None	None	None	I
K/N	0.7266	likely_pathogenic	0.7345	pathogenic	-0.126	Destabilizing	0.997	D	0.579	neutral	N	0.510529401	None	None	I
K/P	0.6972	likely_pathogenic	0.7081	pathogenic	0.169	Stabilizing	0.999	D	0.54	neutral	None	None	None	None	I
K/Q	0.3044	likely_benign	0.3244	benign	-0.198	Destabilizing	0.994	D	0.587	neutral	N	0.501467201	None	None	I
K/R	0.0997	likely_benign	0.1101	benign	-0.158	Destabilizing	0.121	N	0.417	neutral	N	0.464757039	None	None	I
K/S	0.7234	likely_pathogenic	0.7229	pathogenic	-0.502	Destabilizing	0.992	D	0.533	neutral	None	None	None	None	I
K/T	0.3832	ambiguous	0.3888	ambiguous	-0.327	Destabilizing	0.997	D	0.519	neutral	N	0.505507583	None	None	I
K/V	0.5748	likely_pathogenic	0.6193	pathogenic	0.169	Stabilizing	0.998	D	0.553	neutral	None	None	None	None	I
K/W	0.9303	likely_pathogenic	0.954	pathogenic	-0.45	Destabilizing	1.0	D	0.722	prob.delet.	None	None	None	None	I
K/Y	0.8739	likely_pathogenic	0.9003	pathogenic	-0.104	Destabilizing	0.999	D	0.589	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.