TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26493	79702;79703;79704	chr2:178566655;178566654;178566653	chr2:179431382;179431381;179431380
N2AB	24852	74779;74780;74781	chr2:178566655;178566654;178566653	chr2:179431382;179431381;179431380
N2A	23925	71998;71999;72000	chr2:178566655;178566654;178566653	chr2:179431382;179431381;179431380
N2B	17428	52507;52508;52509	chr2:178566655;178566654;178566653	chr2:179431382;179431381;179431380
Novex-1	17553	52882;52883;52884	chr2:178566655;178566654;178566653	chr2:179431382;179431381;179431380
Novex-2	17620	53083;53084;53085	chr2:178566655;178566654;178566653	chr2:179431382;179431381;179431380
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-81
• Domain position: 7
• Structural Position: 7
• Q(SASA): 0.3331
• 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
N/S	None	None	0.999	N	0.557	0.451	0.225902525712	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
N/A	0.2096	likely_benign	0.2217	benign	-0.35	Destabilizing	1.0	D	0.752	deleterious	None	None	None	None	I
N/C	0.2491	likely_benign	0.273	benign	0.497	Stabilizing	1.0	D	0.796	deleterious	None	None	None	None	I
N/D	0.2817	likely_benign	0.3024	benign	-0.084	Destabilizing	0.999	D	0.597	neutral	N	0.508422098	None	None	I
N/E	0.6145	likely_pathogenic	0.6627	pathogenic	-0.116	Destabilizing	0.999	D	0.703	prob.neutral	None	None	None	None	I
N/F	0.4967	ambiguous	0.5269	ambiguous	-0.665	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	I
N/G	0.2618	likely_benign	0.2664	benign	-0.539	Destabilizing	0.999	D	0.574	neutral	None	None	None	None	I
N/H	0.1269	likely_benign	0.1318	benign	-0.625	Destabilizing	1.0	D	0.677	prob.neutral	N	0.496926368	None	None	I
N/I	0.2641	likely_benign	0.295	benign	0.067	Stabilizing	1.0	D	0.845	deleterious	N	0.488025598	None	None	I
N/K	0.5233	ambiguous	0.5653	pathogenic	0.014	Stabilizing	1.0	D	0.714	prob.delet.	N	0.471290648	None	None	I
N/L	0.2743	likely_benign	0.3121	benign	0.067	Stabilizing	1.0	D	0.823	deleterious	None	None	None	None	I
N/M	0.3409	ambiguous	0.3675	ambiguous	0.529	Stabilizing	1.0	D	0.772	deleterious	None	None	None	None	I
N/P	0.7343	likely_pathogenic	0.7585	pathogenic	-0.045	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	I
N/Q	0.4388	ambiguous	0.4794	ambiguous	-0.353	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	I
N/R	0.5242	ambiguous	0.5455	ambiguous	0.078	Stabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	I
N/S	0.085	likely_benign	0.0857	benign	-0.107	Destabilizing	0.999	D	0.557	neutral	N	0.511867835	None	None	I
N/T	0.1558	likely_benign	0.172	benign	-0.004	Destabilizing	0.999	D	0.695	prob.neutral	D	0.528472083	None	None	I
N/V	0.2232	likely_benign	0.25	benign	-0.045	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	I
N/W	0.8029	likely_pathogenic	0.8309	pathogenic	-0.651	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	I
N/Y	0.1893	likely_benign	0.2038	benign	-0.402	Destabilizing	1.0	D	0.816	deleterious	D	0.526640418	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.