TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9179	27760;27761;27762	chr2:178712387;178712386;178712385	chr2:179577114;179577113;179577112
N2AB	8862	26809;26810;26811	chr2:178712387;178712386;178712385	chr2:179577114;179577113;179577112
N2A	7935	24028;24029;24030	chr2:178712387;178712386;178712385	chr2:179577114;179577113;179577112
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: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-77
• Domain position: 68
• Structural Position: 151
• Q(SASA): 0.2572
• 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
A/V	rs1377122264	None	0.002	N	0.319	0.245	0.509996732195	gnomAD-4.0.0	8.89464E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.16928E-05	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
A/C	0.5332	ambiguous	0.4417	ambiguous	-0.873	Destabilizing	0.824	D	0.511	neutral	None	None	None	None	N
A/D	0.2791	likely_benign	0.2282	benign	-0.674	Destabilizing	0.001	N	0.358	neutral	None	None	None	None	N
A/E	0.2062	likely_benign	0.1721	benign	-0.69	Destabilizing	0.062	N	0.518	neutral	N	0.519588815	None	None	N
A/F	0.3265	likely_benign	0.243	benign	-0.933	Destabilizing	0.555	D	0.59	neutral	None	None	None	None	N
A/G	0.132	likely_benign	0.1185	benign	-1.106	Destabilizing	0.027	N	0.466	neutral	D	0.533944978	None	None	N
A/H	0.4817	ambiguous	0.397	ambiguous	-1.243	Destabilizing	0.824	D	0.567	neutral	None	None	None	None	N
A/I	0.2598	likely_benign	0.2002	benign	-0.248	Destabilizing	0.081	N	0.501	neutral	None	None	None	None	N
A/K	0.3844	ambiguous	0.3041	benign	-1.002	Destabilizing	0.081	N	0.498	neutral	None	None	None	None	N
A/L	0.2205	likely_benign	0.173	benign	-0.248	Destabilizing	0.081	N	0.504	neutral	None	None	None	None	N
A/M	0.2324	likely_benign	0.193	benign	-0.246	Destabilizing	0.555	D	0.527	neutral	None	None	None	None	N
A/N	0.2652	likely_benign	0.211	benign	-0.762	Destabilizing	0.081	N	0.559	neutral	None	None	None	None	N
A/P	0.7436	likely_pathogenic	0.6064	pathogenic	-0.401	Destabilizing	None	N	0.288	neutral	N	0.52001887	None	None	N
A/Q	0.303	likely_benign	0.2621	benign	-0.862	Destabilizing	0.005	N	0.275	neutral	None	None	None	None	N
A/R	0.3196	likely_benign	0.2582	benign	-0.75	Destabilizing	0.235	N	0.532	neutral	None	None	None	None	N
A/S	0.09	likely_benign	0.0823	benign	-1.204	Destabilizing	None	N	0.345	neutral	N	0.458444355	None	None	N
A/T	0.0944	likely_benign	0.0839	benign	-1.109	Destabilizing	0.062	N	0.465	neutral	D	0.523823985	None	None	N
A/V	0.1499	likely_benign	0.1245	benign	-0.401	Destabilizing	0.002	N	0.319	neutral	N	0.5097882	None	None	N
A/W	0.7081	likely_pathogenic	0.6002	pathogenic	-1.277	Destabilizing	0.935	D	0.647	neutral	None	None	None	None	N
A/Y	0.4259	ambiguous	0.3287	benign	-0.847	Destabilizing	0.555	D	0.591	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.