TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25161	75706;75707;75708	chr2:178570651;178570650;178570649	chr2:179435378;179435377;179435376
N2AB	23520	70783;70784;70785	chr2:178570651;178570650;178570649	chr2:179435378;179435377;179435376
N2A	22593	68002;68003;68004	chr2:178570651;178570650;178570649	chr2:179435378;179435377;179435376
N2B	16096	48511;48512;48513	chr2:178570651;178570650;178570649	chr2:179435378;179435377;179435376
Novex-1	16221	48886;48887;48888	chr2:178570651;178570650;178570649	chr2:179435378;179435377;179435376
Novex-2	16288	49087;49088;49089	chr2:178570651;178570650;178570649	chr2:179435378;179435377;179435376
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-134
• Domain position: 51
• Structural Position: 125
• Q(SASA): 0.7584
• 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
K/N	rs1707854232	0.485	0.942	N	0.5	0.427	0.275641507738	gnomAD-4.0.0	4.10597E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.49786E-06	1.15945E-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
K/A	0.3144	likely_benign	0.3275	benign	-0.113	Destabilizing	0.86	D	0.541	neutral	None	None	None	None	N
K/C	0.4841	ambiguous	0.5397	ambiguous	-0.244	Destabilizing	0.998	D	0.695	prob.neutral	None	None	None	None	N
K/D	0.5698	likely_pathogenic	0.6104	pathogenic	0.271	Stabilizing	0.978	D	0.559	neutral	None	None	None	None	N
K/E	0.184	likely_benign	0.1903	benign	0.258	Stabilizing	0.822	D	0.527	neutral	N	0.490711489	None	None	N
K/F	0.6012	likely_pathogenic	0.6477	pathogenic	-0.513	Destabilizing	0.956	D	0.685	prob.neutral	None	None	None	None	N
K/G	0.4972	ambiguous	0.5141	ambiguous	-0.269	Destabilizing	0.926	D	0.531	neutral	None	None	None	None	N
K/H	0.1954	likely_benign	0.2101	benign	-0.682	Destabilizing	0.043	N	0.421	neutral	None	None	None	None	N
K/I	0.2167	likely_benign	0.2302	benign	0.209	Stabilizing	0.915	D	0.679	prob.neutral	None	None	None	None	N
K/L	0.2831	likely_benign	0.3139	benign	0.209	Stabilizing	0.514	D	0.54	neutral	None	None	None	None	N
K/M	0.189	likely_benign	0.2042	benign	0.243	Stabilizing	0.489	N	0.449	neutral	N	0.502826441	None	None	N
K/N	0.368	ambiguous	0.3937	ambiguous	0.327	Stabilizing	0.942	D	0.5	neutral	N	0.513333372	None	None	N
K/P	0.9332	likely_pathogenic	0.9457	pathogenic	0.128	Stabilizing	0.993	D	0.611	neutral	None	None	None	None	N
K/Q	0.1114	likely_benign	0.1119	benign	0.076	Stabilizing	0.97	D	0.55	neutral	N	0.497157459	None	None	N
K/R	0.0768	likely_benign	0.0779	benign	0.075	Stabilizing	0.822	D	0.499	neutral	N	0.516916656	None	None	N
K/S	0.3456	ambiguous	0.3669	ambiguous	-0.233	Destabilizing	0.86	D	0.517	neutral	None	None	None	None	N
K/T	0.1305	likely_benign	0.135	benign	-0.106	Destabilizing	0.942	D	0.533	neutral	N	0.473144449	None	None	N
K/V	0.2236	likely_benign	0.2405	benign	0.128	Stabilizing	0.754	D	0.527	neutral	None	None	None	None	N
K/W	0.6334	likely_pathogenic	0.6682	pathogenic	-0.483	Destabilizing	0.998	D	0.719	prob.delet.	None	None	None	None	N
K/Y	0.4857	ambiguous	0.5298	ambiguous	-0.099	Destabilizing	0.956	D	0.669	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.