TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26318	79177;79178;79179	chr2:178567180;178567179;178567178	chr2:179431907;179431906;179431905
N2AB	24677	74254;74255;74256	chr2:178567180;178567179;178567178	chr2:179431907;179431906;179431905
N2A	23750	71473;71474;71475	chr2:178567180;178567179;178567178	chr2:179431907;179431906;179431905
N2B	17253	51982;51983;51984	chr2:178567180;178567179;178567178	chr2:179431907;179431906;179431905
Novex-1	17378	52357;52358;52359	chr2:178567180;178567179;178567178	chr2:179431907;179431906;179431905
Novex-2	17445	52558;52559;52560	chr2:178567180;178567179;178567178	chr2:179431907;179431906;179431905
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Fn3-79
• Domain position: 33
• Structural Position: 34
• Q(SASA): 0.6723
• 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
D/N	rs772799438	0.665	0.004	N	0.266	0.108	0.158396225186	gnomAD-2.1.1	8.08E-06	None	None	None	None	I	None	0	0	None	0	0	None	6.55E-05	None	0	0	0
D/N	rs772799438	0.665	0.004	N	0.266	0.108	0.158396225186	gnomAD-4.0.0	2.05333E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	3.47971E-05	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
D/A	0.0982	likely_benign	0.1038	benign	-0.054	Destabilizing	0.201	N	0.485	neutral	N	0.444175831	None	None	I
D/C	0.48	ambiguous	0.511	ambiguous	0.328	Stabilizing	0.992	D	0.461	neutral	None	None	None	None	I
D/E	0.1072	likely_benign	0.1146	benign	-0.131	Destabilizing	0.004	N	0.134	neutral	N	0.405462727	None	None	I
D/F	0.5092	ambiguous	0.5227	ambiguous	-0.257	Destabilizing	0.972	D	0.471	neutral	None	None	None	None	I
D/G	0.1421	likely_benign	0.1591	benign	-0.182	Destabilizing	0.002	N	0.144	neutral	N	0.458779924	None	None	I
D/H	0.2317	likely_benign	0.2369	benign	-0.046	Destabilizing	0.81	D	0.437	neutral	N	0.484638374	None	None	I
D/I	0.2315	likely_benign	0.2393	benign	0.214	Stabilizing	0.92	D	0.491	neutral	None	None	None	None	I
D/K	0.2533	likely_benign	0.2544	benign	0.623	Stabilizing	0.447	N	0.441	neutral	None	None	None	None	I
D/L	0.2615	likely_benign	0.2732	benign	0.214	Stabilizing	0.617	D	0.463	neutral	None	None	None	None	I
D/M	0.4262	ambiguous	0.4402	ambiguous	0.354	Stabilizing	0.992	D	0.455	neutral	None	None	None	None	I
D/N	0.0876	likely_benign	0.0907	benign	0.484	Stabilizing	0.004	N	0.266	neutral	N	0.492911141	None	None	I
D/P	0.3393	likely_benign	0.3355	benign	0.145	Stabilizing	0.92	D	0.448	neutral	None	None	None	None	I
D/Q	0.2289	likely_benign	0.238	benign	0.482	Stabilizing	0.739	D	0.366	neutral	None	None	None	None	I
D/R	0.316	likely_benign	0.3252	benign	0.626	Stabilizing	0.85	D	0.451	neutral	None	None	None	None	I
D/S	0.0931	likely_benign	0.0989	benign	0.391	Stabilizing	0.026	N	0.066	neutral	None	None	None	None	I
D/T	0.152	likely_benign	0.1592	benign	0.49	Stabilizing	0.447	N	0.447	neutral	None	None	None	None	I
D/V	0.1348	likely_benign	0.1392	benign	0.145	Stabilizing	0.896	D	0.463	neutral	D	0.523983409	None	None	I
D/W	0.8775	likely_pathogenic	0.8728	pathogenic	-0.233	Destabilizing	0.992	D	0.58	neutral	None	None	None	None	I
D/Y	0.2368	likely_benign	0.2488	benign	-0.038	Destabilizing	0.963	D	0.472	neutral	N	0.481777265	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.