TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25879	77860;77861;77862	chr2:178568497;178568496;178568495	chr2:179433224;179433223;179433222
N2AB	24238	72937;72938;72939	chr2:178568497;178568496;178568495	chr2:179433224;179433223;179433222
N2A	23311	70156;70157;70158	chr2:178568497;178568496;178568495	chr2:179433224;179433223;179433222
N2B	16814	50665;50666;50667	chr2:178568497;178568496;178568495	chr2:179433224;179433223;179433222
Novex-1	16939	51040;51041;51042	chr2:178568497;178568496;178568495	chr2:179433224;179433223;179433222
Novex-2	17006	51241;51242;51243	chr2:178568497;178568496;178568495	chr2:179433224;179433223;179433222
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-136
• Domain position: 82
• Structural Position: 166
• Q(SASA): 0.3552
• 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/R	None	None	0.892	N	0.526	0.161	0.423716096872	gnomAD-4.0.0	1.59203E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85958E-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	0.3546	ambiguous	0.3303	benign	-0.446	Destabilizing	0.916	D	0.597	neutral	None	None	None	None	I
K/C	0.576	likely_pathogenic	0.548	ambiguous	-0.496	Destabilizing	0.999	D	0.769	deleterious	None	None	None	None	I
K/D	0.6664	likely_pathogenic	0.6552	pathogenic	-0.117	Destabilizing	0.845	D	0.639	neutral	None	None	None	None	I
K/E	0.2309	likely_benign	0.2235	benign	-0.036	Destabilizing	0.805	D	0.552	neutral	N	0.500272335	None	None	I
K/F	0.8217	likely_pathogenic	0.798	pathogenic	-0.151	Destabilizing	0.996	D	0.746	deleterious	None	None	None	None	I
K/G	0.5632	ambiguous	0.5355	ambiguous	-0.788	Destabilizing	0.845	D	0.645	neutral	None	None	None	None	I
K/H	0.322	likely_benign	0.3099	benign	-1.105	Destabilizing	0.987	D	0.658	neutral	None	None	None	None	I
K/I	0.4082	ambiguous	0.3556	ambiguous	0.427	Stabilizing	0.987	D	0.753	deleterious	None	None	None	None	I
K/L	0.4341	ambiguous	0.4063	ambiguous	0.427	Stabilizing	0.975	D	0.65	neutral	None	None	None	None	I
K/M	0.2519	likely_benign	0.2288	benign	0.283	Stabilizing	0.999	D	0.64	neutral	N	0.487480436	None	None	I
K/N	0.4292	ambiguous	0.4047	ambiguous	-0.341	Destabilizing	0.056	N	0.287	neutral	N	0.52114904	None	None	I
K/P	0.9615	likely_pathogenic	0.9624	pathogenic	0.167	Stabilizing	0.996	D	0.677	prob.neutral	None	None	None	None	I
K/Q	0.1347	likely_benign	0.1321	benign	-0.47	Destabilizing	0.426	N	0.273	neutral	N	0.499984334	None	None	I
K/R	0.0898	likely_benign	0.0902	benign	-0.584	Destabilizing	0.892	D	0.526	neutral	N	0.504544791	None	None	I
K/S	0.4336	ambiguous	0.4068	ambiguous	-0.966	Destabilizing	0.845	D	0.547	neutral	None	None	None	None	I
K/T	0.1916	likely_benign	0.1724	benign	-0.696	Destabilizing	0.892	D	0.639	neutral	N	0.469797499	None	None	I
K/V	0.318	likely_benign	0.2876	benign	0.167	Stabilizing	0.987	D	0.656	neutral	None	None	None	None	I
K/W	0.8404	likely_pathogenic	0.828	pathogenic	-0.019	Destabilizing	0.999	D	0.726	prob.delet.	None	None	None	None	I
K/Y	0.6717	likely_pathogenic	0.6454	pathogenic	0.251	Stabilizing	0.996	D	0.753	deleterious	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.