TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25478	76657;76658;76659	chr2:178569700;178569699;178569698	chr2:179434427;179434426;179434425
N2AB	23837	71734;71735;71736	chr2:178569700;178569699;178569698	chr2:179434427;179434426;179434425
N2A	22910	68953;68954;68955	chr2:178569700;178569699;178569698	chr2:179434427;179434426;179434425
N2B	16413	49462;49463;49464	chr2:178569700;178569699;178569698	chr2:179434427;179434426;179434425
Novex-1	16538	49837;49838;49839	chr2:178569700;178569699;178569698	chr2:179434427;179434426;179434425
Novex-2	16605	50038;50039;50040	chr2:178569700;178569699;178569698	chr2:179434427;179434426;179434425
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: Fn3-73
• Domain position: 74
• Structural Position: 105
• Q(SASA): 0.3223
• 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/D	rs752247447	-1.689	0.285	N	0.522	0.126	0.214338557667	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
N/D	rs752247447	-1.689	0.285	N	0.522	0.126	0.214338557667	gnomAD-4.0.0	3.18589E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.86714E-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
N/A	0.1758	likely_benign	0.1695	benign	-1.158	Destabilizing	0.209	N	0.49	neutral	None	None	None	None	N
N/C	0.1348	likely_benign	0.1386	benign	-0.301	Destabilizing	0.991	D	0.605	neutral	None	None	None	None	N
N/D	0.178	likely_benign	0.1734	benign	-1.653	Destabilizing	0.285	N	0.522	neutral	N	0.50420557	None	None	N
N/E	0.2854	likely_benign	0.2752	benign	-1.349	Destabilizing	0.103	N	0.397	neutral	None	None	None	None	N
N/F	0.3378	likely_benign	0.3479	ambiguous	-0.492	Destabilizing	0.901	D	0.585	neutral	None	None	None	None	N
N/G	0.2957	likely_benign	0.2898	benign	-1.593	Destabilizing	0.345	N	0.463	neutral	None	None	None	None	N
N/H	0.0604	likely_benign	0.0614	benign	-0.777	Destabilizing	0.003	N	0.337	neutral	N	0.469458278	None	None	N
N/I	0.1077	likely_benign	0.1088	benign	0.045	Stabilizing	0.873	D	0.602	neutral	N	0.470535713	None	None	N
N/K	0.1214	likely_benign	0.1161	benign	0.045	Stabilizing	None	N	0.228	neutral	N	0.406561592	None	None	N
N/L	0.1294	likely_benign	0.1304	benign	0.045	Stabilizing	0.345	N	0.553	neutral	None	None	None	None	N
N/M	0.1923	likely_benign	0.1951	benign	0.044	Stabilizing	0.965	D	0.567	neutral	None	None	None	None	N
N/P	0.8997	likely_pathogenic	0.8584	pathogenic	-0.332	Destabilizing	0.722	D	0.561	neutral	None	None	None	None	N
N/Q	0.1579	likely_benign	0.1561	benign	-0.42	Destabilizing	0.021	N	0.231	neutral	None	None	None	None	N
N/R	0.1287	likely_benign	0.127	benign	-0.239	Destabilizing	0.209	N	0.488	neutral	None	None	None	None	N
N/S	0.0743	likely_benign	0.0743	benign	-1.128	Destabilizing	0.285	N	0.461	neutral	N	0.436479068	None	None	N
N/T	0.0846	likely_benign	0.084	benign	-0.63	Destabilizing	0.285	N	0.527	neutral	N	0.444866477	None	None	N
N/V	0.118	likely_benign	0.1188	benign	-0.332	Destabilizing	0.561	D	0.57	neutral	None	None	None	None	N
N/W	0.6042	likely_pathogenic	0.5954	pathogenic	-0.38	Destabilizing	0.991	D	0.622	neutral	None	None	None	None	N
N/Y	0.0976	likely_benign	0.098	benign	-0.008	Destabilizing	0.326	N	0.6	neutral	N	0.465052536	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.