TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5782	17569;17570;17571	chr2:178731422;178731421;178731420	chr2:179596149;179596148;179596147
N2AB	5465	16618;16619;16620	chr2:178731422;178731421;178731420	chr2:179596149;179596148;179596147
N2A	4538	13837;13838;13839	chr2:178731422;178731421;178731420	chr2:179596149;179596148;179596147
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: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Ig-41
• Domain position: 53
• Structural Position: 131
• Q(SASA): 0.8622
• 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
N/K	rs535281449	0.343	0.98	N	0.385	0.19	0.177238962908	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.88E-06	0
N/S	rs1423767140	0.246	0.659	N	0.222	0.165	0.128392430309	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.88E-06	0
N/S	rs1423767140	0.246	0.659	N	0.222	0.165	0.128392430309	gnomAD-4.0.0	1.59123E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85812E-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	0.3755	ambiguous	0.3627	ambiguous	-0.057	Destabilizing	0.971	D	0.429	neutral	None	None	None	None	N
N/C	0.506	ambiguous	0.4914	ambiguous	0.105	Stabilizing	1.0	D	0.524	neutral	None	None	None	None	N
N/D	0.1024	likely_benign	0.0996	benign	0.084	Stabilizing	0.135	N	0.183	neutral	N	0.464537169	None	None	N
N/E	0.3223	likely_benign	0.3044	benign	0.024	Stabilizing	0.971	D	0.359	neutral	None	None	None	None	N
N/F	0.7638	likely_pathogenic	0.7546	pathogenic	-0.659	Destabilizing	0.998	D	0.488	neutral	None	None	None	None	N
N/G	0.2807	likely_benign	0.2748	benign	-0.152	Destabilizing	0.985	D	0.371	neutral	None	None	None	None	N
N/H	0.1475	likely_benign	0.1436	benign	-0.161	Destabilizing	0.265	N	0.268	neutral	N	0.512389831	None	None	N
N/I	0.613	likely_pathogenic	0.6181	pathogenic	0.089	Stabilizing	0.997	D	0.487	neutral	N	0.461883859	None	None	N
N/K	0.2735	likely_benign	0.2566	benign	0.087	Stabilizing	0.98	D	0.385	neutral	N	0.497612379	None	None	N
N/L	0.5319	ambiguous	0.5251	ambiguous	0.089	Stabilizing	0.998	D	0.455	neutral	None	None	None	None	N
N/M	0.5304	ambiguous	0.5226	ambiguous	0.086	Stabilizing	1.0	D	0.479	neutral	None	None	None	None	N
N/P	0.9045	likely_pathogenic	0.8997	pathogenic	0.064	Stabilizing	0.998	D	0.467	neutral	None	None	None	None	N
N/Q	0.3157	likely_benign	0.305	benign	-0.306	Destabilizing	0.998	D	0.359	neutral	None	None	None	None	N
N/R	0.3455	ambiguous	0.3275	benign	0.151	Stabilizing	0.998	D	0.351	neutral	None	None	None	None	N
N/S	0.1366	likely_benign	0.1379	benign	-0.077	Destabilizing	0.659	D	0.222	neutral	N	0.470617779	None	None	N
N/T	0.2928	likely_benign	0.289	benign	-0.025	Destabilizing	0.961	D	0.357	neutral	N	0.500999401	None	None	N
N/V	0.5873	likely_pathogenic	0.5914	pathogenic	0.064	Stabilizing	0.998	D	0.495	neutral	None	None	None	None	N
N/W	0.825	likely_pathogenic	0.8118	pathogenic	-0.805	Destabilizing	1.0	D	0.611	neutral	None	None	None	None	N
N/Y	0.2418	likely_benign	0.2351	benign	-0.473	Destabilizing	0.994	D	0.461	neutral	N	0.461883859	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.