TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34389	103390;103391;103392	chr2:178533450;178533449;178533448	chr2:179398177;179398176;179398175
N2AB	32748	98467;98468;98469	chr2:178533450;178533449;178533448	chr2:179398177;179398176;179398175
N2A	31821	95686;95687;95688	chr2:178533450;178533449;178533448	chr2:179398177;179398176;179398175
N2B	25324	76195;76196;76197	chr2:178533450;178533449;178533448	chr2:179398177;179398176;179398175
Novex-1	25449	76570;76571;76572	chr2:178533450;178533449;178533448	chr2:179398177;179398176;179398175
Novex-2	25516	76771;76772;76773	chr2:178533450;178533449;178533448	chr2:179398177;179398176;179398175
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-162
• Domain position: 27
• Structural Position: 41
• Q(SASA): 0.6215
• 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
I/V	rs796349969	None	0.022	N	0.234	0.098	0.437850553699	gnomAD-4.0.0	3.18283E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.71716E-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
I/A	0.7348	likely_pathogenic	0.5206	ambiguous	-0.454	Destabilizing	0.525	D	0.411	neutral	None	None	None	None	I
I/C	0.8813	likely_pathogenic	0.7677	pathogenic	-0.612	Destabilizing	0.998	D	0.459	neutral	None	None	None	None	I
I/D	0.8639	likely_pathogenic	0.7223	pathogenic	-0.323	Destabilizing	0.842	D	0.515	neutral	None	None	None	None	I
I/E	0.7814	likely_pathogenic	0.6216	pathogenic	-0.424	Destabilizing	0.842	D	0.535	neutral	None	None	None	None	I
I/F	0.2403	likely_benign	0.1607	benign	-0.618	Destabilizing	0.966	D	0.379	neutral	N	0.4563482	None	None	I
I/G	0.937	likely_pathogenic	0.8242	pathogenic	-0.573	Destabilizing	0.842	D	0.529	neutral	None	None	None	None	I
I/H	0.6787	likely_pathogenic	0.4718	ambiguous	0.091	Stabilizing	0.998	D	0.503	neutral	None	None	None	None	I
I/K	0.653	likely_pathogenic	0.4427	ambiguous	-0.292	Destabilizing	0.842	D	0.526	neutral	None	None	None	None	I
I/L	0.1871	likely_benign	0.129	benign	-0.268	Destabilizing	0.267	N	0.252	neutral	N	0.490479416	None	None	I
I/M	0.1656	likely_benign	0.113	benign	-0.459	Destabilizing	0.966	D	0.387	neutral	D	0.524669347	None	None	I
I/N	0.3953	ambiguous	0.2332	benign	-0.089	Destabilizing	0.934	D	0.51	neutral	N	0.454422615	None	None	I
I/P	0.9771	likely_pathogenic	0.9526	pathogenic	-0.3	Destabilizing	0.974	D	0.519	neutral	None	None	None	None	I
I/Q	0.6514	likely_pathogenic	0.4555	ambiguous	-0.313	Destabilizing	0.974	D	0.522	neutral	None	None	None	None	I
I/R	0.6078	likely_pathogenic	0.3907	ambiguous	0.239	Stabilizing	0.949	D	0.52	neutral	None	None	None	None	I
I/S	0.5309	ambiguous	0.3257	benign	-0.462	Destabilizing	0.136	N	0.359	neutral	N	0.423542348	None	None	I
I/T	0.4643	ambiguous	0.2756	benign	-0.461	Destabilizing	0.051	N	0.271	neutral	N	0.465119612	None	None	I
I/V	0.1319	likely_benign	0.0943	benign	-0.3	Destabilizing	0.022	N	0.234	neutral	N	0.466909123	None	None	I
I/W	0.8903	likely_pathogenic	0.8144	pathogenic	-0.64	Destabilizing	0.998	D	0.547	neutral	None	None	None	None	I
I/Y	0.6316	likely_pathogenic	0.4901	ambiguous	-0.388	Destabilizing	0.991	D	0.458	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.