TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25570	76933;76934;76935	chr2:178569424;178569423;178569422	chr2:179434151;179434150;179434149
N2AB	23929	72010;72011;72012	chr2:178569424;178569423;178569422	chr2:179434151;179434150;179434149
N2A	23002	69229;69230;69231	chr2:178569424;178569423;178569422	chr2:179434151;179434150;179434149
N2B	16505	49738;49739;49740	chr2:178569424;178569423;178569422	chr2:179434151;179434150;179434149
Novex-1	16630	50113;50114;50115	chr2:178569424;178569423;178569422	chr2:179434151;179434150;179434149
Novex-2	16697	50314;50315;50316	chr2:178569424;178569423;178569422	chr2:179434151;179434150;179434149
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-135
• Domain position: 57
• Structural Position: 143
• Q(SASA): 0.5378
• 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	None	None	0.698	N	0.371	0.159	0.0762999501168	gnomAD-4.0.0	1.59235E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43406E-05	0
N/S	None	None	0.058	N	0.331	0.137	0.115124310173	gnomAD-4.0.0	1.59235E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85984E-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	0.2031	likely_benign	0.2179	benign	-0.418	Destabilizing	0.754	D	0.405	neutral	None	None	None	None	N
N/C	0.2286	likely_benign	0.2528	benign	0.38	Stabilizing	0.998	D	0.658	neutral	None	None	None	None	N
N/D	0.118	likely_benign	0.1218	benign	0.046	Stabilizing	0.822	D	0.411	neutral	N	0.484723227	None	None	N
N/E	0.3248	likely_benign	0.3571	ambiguous	-0.002	Destabilizing	0.754	D	0.37	neutral	None	None	None	None	N
N/F	0.4645	ambiguous	0.5214	ambiguous	-0.87	Destabilizing	0.993	D	0.626	neutral	None	None	None	None	N
N/G	0.2377	likely_benign	0.2464	benign	-0.564	Destabilizing	0.754	D	0.383	neutral	None	None	None	None	N
N/H	0.0876	likely_benign	0.0982	benign	-0.65	Destabilizing	0.97	D	0.409	neutral	N	0.48313212	None	None	N
N/I	0.2746	likely_benign	0.3042	benign	-0.12	Destabilizing	0.97	D	0.623	neutral	N	0.49336279	None	None	N
N/K	0.2259	likely_benign	0.2633	benign	0.217	Stabilizing	0.698	D	0.371	neutral	N	0.48999576	None	None	N
N/L	0.2766	likely_benign	0.3077	benign	-0.12	Destabilizing	0.956	D	0.516	neutral	None	None	None	None	N
N/M	0.3205	likely_benign	0.345	ambiguous	0.406	Stabilizing	0.994	D	0.567	neutral	None	None	None	None	N
N/P	0.8115	likely_pathogenic	0.8221	pathogenic	-0.194	Destabilizing	0.978	D	0.569	neutral	None	None	None	None	N
N/Q	0.2588	likely_benign	0.2877	benign	-0.311	Destabilizing	0.16	N	0.301	neutral	None	None	None	None	N
N/R	0.257	likely_benign	0.2964	benign	0.313	Stabilizing	0.915	D	0.383	neutral	None	None	None	None	N
N/S	0.083	likely_benign	0.0844	benign	-0.04	Destabilizing	0.058	N	0.331	neutral	N	0.512987263	None	None	N
N/T	0.134	likely_benign	0.1443	benign	0.051	Stabilizing	0.698	D	0.371	neutral	N	0.471775815	None	None	N
N/V	0.253	likely_benign	0.2767	benign	-0.194	Destabilizing	0.956	D	0.611	neutral	None	None	None	None	N
N/W	0.7801	likely_pathogenic	0.8136	pathogenic	-0.829	Destabilizing	0.998	D	0.674	neutral	None	None	None	None	N
N/Y	0.1607	likely_benign	0.1844	benign	-0.559	Destabilizing	0.99	D	0.582	neutral	N	0.492855811	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.