TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5265	16018;16019;16020	chr2:178733500;178733499;178733498	chr2:179598227;179598226;179598225
N2AB	4948	15067;15068;15069	chr2:178733500;178733499;178733498	chr2:179598227;179598226;179598225
N2A	4021	12286;12287;12288	chr2:178733500;178733499;178733498	chr2:179598227;179598226;179598225
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-36
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.5667
• Predicted PPI site: N

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/K	rs1370636944	0.427	0.024	D	0.353	0.259	0.31291088546	gnomAD-2.1.1	3.18E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
E/K	rs1370636944	0.427	0.024	D	0.353	0.259	0.31291088546	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/K	rs1370636944	0.427	0.024	D	0.353	0.259	0.31291088546	gnomAD-4.0.0	4.34592E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.94335E-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
E/A	0.2532	likely_benign	0.2989	benign	-0.431	Destabilizing	0.645	D	0.505	neutral	D	0.565495695	None	None	N
E/C	0.9048	likely_pathogenic	0.9331	pathogenic	-0.233	Destabilizing	0.995	D	0.661	neutral	None	None	None	None	N
E/D	0.1759	likely_benign	0.1924	benign	-0.446	Destabilizing	0.006	N	0.285	neutral	N	0.511406596	None	None	N
E/F	0.868	likely_pathogenic	0.9125	pathogenic	-0.126	Destabilizing	0.995	D	0.629	neutral	None	None	None	None	N
E/G	0.2136	likely_benign	0.261	benign	-0.657	Destabilizing	0.645	D	0.481	neutral	D	0.597637375	None	None	N
E/H	0.5272	ambiguous	0.5847	pathogenic	0.146	Stabilizing	0.985	D	0.526	neutral	None	None	None	None	N
E/I	0.6395	likely_pathogenic	0.7449	pathogenic	0.14	Stabilizing	0.945	D	0.646	neutral	None	None	None	None	N
E/K	0.1902	likely_benign	0.2308	benign	0.241	Stabilizing	0.024	N	0.353	neutral	D	0.53821979	None	None	N
E/L	0.6112	likely_pathogenic	0.7143	pathogenic	0.14	Stabilizing	0.945	D	0.621	neutral	None	None	None	None	N
E/M	0.6967	likely_pathogenic	0.7799	pathogenic	0.149	Stabilizing	0.995	D	0.591	neutral	None	None	None	None	N
E/N	0.352	ambiguous	0.4062	ambiguous	-0.261	Destabilizing	0.809	D	0.476	neutral	None	None	None	None	N
E/P	0.9079	likely_pathogenic	0.9453	pathogenic	-0.03	Destabilizing	0.945	D	0.573	neutral	None	None	None	None	N
E/Q	0.1545	likely_benign	0.1747	benign	-0.191	Destabilizing	0.864	D	0.467	neutral	D	0.561506871	None	None	N
E/R	0.3208	likely_benign	0.3686	ambiguous	0.527	Stabilizing	0.809	D	0.493	neutral	None	None	None	None	N
E/S	0.2561	likely_benign	0.2961	benign	-0.397	Destabilizing	0.547	D	0.475	neutral	None	None	None	None	N
E/T	0.3223	likely_benign	0.3903	ambiguous	-0.204	Destabilizing	0.894	D	0.487	neutral	None	None	None	None	N
E/V	0.4193	ambiguous	0.5116	ambiguous	-0.03	Destabilizing	0.928	D	0.585	neutral	D	0.561258876	None	None	N
E/W	0.9417	likely_pathogenic	0.9597	pathogenic	0.081	Stabilizing	0.995	D	0.675	neutral	None	None	None	None	N
E/Y	0.7592	likely_pathogenic	0.821	pathogenic	0.127	Stabilizing	0.981	D	0.597	neutral	None	None	None	None	N

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.