TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25335	76228;76229;76230	chr2:178570129;178570128;178570127	chr2:179434856;179434855;179434854
N2AB	23694	71305;71306;71307	chr2:178570129;178570128;178570127	chr2:179434856;179434855;179434854
N2A	22767	68524;68525;68526	chr2:178570129;178570128;178570127	chr2:179434856;179434855;179434854
N2B	16270	49033;49034;49035	chr2:178570129;178570128;178570127	chr2:179434856;179434855;179434854
Novex-1	16395	49408;49409;49410	chr2:178570129;178570128;178570127	chr2:179434856;179434855;179434854
Novex-2	16462	49609;49610;49611	chr2:178570129;178570128;178570127	chr2:179434856;179434855;179434854
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-72
• Domain position: 32
• Structural Position: 34
• Q(SASA): 0.6653
• 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
E/Q	rs1416617749	0.31	0.959	N	0.362	0.246	0.240491677333	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	0	1.66003E-04
E/Q	rs1416617749	0.31	0.959	N	0.362	0.246	0.240491677333	gnomAD-4.0.0	1.59181E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.02535E-05

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
E/A	0.1615	likely_benign	0.2014	benign	-0.329	Destabilizing	0.061	N	0.137	neutral	N	0.488833472	None	None	I
E/C	0.8431	likely_pathogenic	0.8925	pathogenic	-0.048	Destabilizing	0.999	D	0.395	neutral	None	None	None	None	I
E/D	0.0901	likely_benign	0.1078	benign	-0.279	Destabilizing	0.826	D	0.345	neutral	N	0.503128134	None	None	I
E/F	0.8319	likely_pathogenic	0.8766	pathogenic	-0.169	Destabilizing	0.997	D	0.412	neutral	None	None	None	None	I
E/G	0.2188	likely_benign	0.2541	benign	-0.521	Destabilizing	0.704	D	0.42	neutral	N	0.476803742	None	None	I
E/H	0.5115	ambiguous	0.5842	pathogenic	0.135	Stabilizing	0.997	D	0.363	neutral	None	None	None	None	I
E/I	0.4251	ambiguous	0.5301	ambiguous	0.14	Stabilizing	0.991	D	0.434	neutral	None	None	None	None	I
E/K	0.2036	likely_benign	0.2199	benign	0.415	Stabilizing	0.92	D	0.312	neutral	N	0.502320058	None	None	I
E/L	0.4726	ambiguous	0.5777	pathogenic	0.14	Stabilizing	0.939	D	0.437	neutral	None	None	None	None	I
E/M	0.5309	ambiguous	0.6142	pathogenic	0.183	Stabilizing	0.999	D	0.403	neutral	None	None	None	None	I
E/N	0.2255	likely_benign	0.2763	benign	0.03	Stabilizing	0.939	D	0.352	neutral	None	None	None	None	I
E/P	0.268	likely_benign	0.3487	ambiguous	0.004	Stabilizing	0.02	N	0.125	neutral	None	None	None	None	I
E/Q	0.1735	likely_benign	0.1972	benign	0.076	Stabilizing	0.959	D	0.362	neutral	N	0.473485606	None	None	I
E/R	0.3336	likely_benign	0.3598	ambiguous	0.627	Stabilizing	0.991	D	0.347	neutral	None	None	None	None	I
E/S	0.1992	likely_benign	0.2456	benign	-0.117	Destabilizing	0.373	N	0.173	neutral	None	None	None	None	I
E/T	0.2337	likely_benign	0.2997	benign	0.047	Stabilizing	0.939	D	0.381	neutral	None	None	None	None	I
E/V	0.2463	likely_benign	0.3119	benign	0.004	Stabilizing	0.92	D	0.425	neutral	N	0.487399579	None	None	I
E/W	0.9432	likely_pathogenic	0.9547	pathogenic	-0.009	Destabilizing	0.999	D	0.519	neutral	None	None	None	None	I
E/Y	0.7074	likely_pathogenic	0.7611	pathogenic	0.081	Stabilizing	0.997	D	0.422	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.