TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31026	93301;93302;93303	chr2:178548550;178548549;178548548	chr2:179413277;179413276;179413275
N2AB	29385	88378;88379;88380	chr2:178548550;178548549;178548548	chr2:179413277;179413276;179413275
N2A	28458	85597;85598;85599	chr2:178548550;178548549;178548548	chr2:179413277;179413276;179413275
N2B	21961	66106;66107;66108	chr2:178548550;178548549;178548548	chr2:179413277;179413276;179413275
Novex-1	22086	66481;66482;66483	chr2:178548550;178548549;178548548	chr2:179413277;179413276;179413275
Novex-2	22153	66682;66683;66684	chr2:178548550;178548549;178548548	chr2:179413277;179413276;179413275
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-114
• Domain position: 11
• Structural Position: 13
• Q(SASA): 0.3699
• 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/E	rs759887010	0.572	0.939	N	0.441	0.251	0.277730125212	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	5.57E-05	None	0	None	0	0	0
K/E	rs759887010	0.572	0.939	N	0.441	0.251	0.277730125212	gnomAD-4.0.0	1.59113E-06	None	None	None	None	N	None	0	0	None	0	2.77269E-05	None	0	0	0	0	0
K/R	rs1698120195	None	0.046	N	0.195	0.128	0.270447802918	gnomAD-4.0.0	2.05255E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69836E-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
K/A	0.9108	likely_pathogenic	0.8148	pathogenic	0.059	Stabilizing	0.953	D	0.573	neutral	None	None	None	None	N
K/C	0.9337	likely_pathogenic	0.8915	pathogenic	-0.271	Destabilizing	0.999	D	0.785	deleterious	None	None	None	None	N
K/D	0.9758	likely_pathogenic	0.9424	pathogenic	-0.109	Destabilizing	0.993	D	0.749	deleterious	None	None	None	None	N
K/E	0.8448	likely_pathogenic	0.6801	pathogenic	-0.11	Destabilizing	0.939	D	0.441	neutral	N	0.51315034	None	None	N
K/F	0.9867	likely_pathogenic	0.9705	pathogenic	-0.203	Destabilizing	0.999	D	0.79	deleterious	None	None	None	None	N
K/G	0.9275	likely_pathogenic	0.8552	pathogenic	-0.113	Destabilizing	0.993	D	0.703	prob.neutral	None	None	None	None	N
K/H	0.6923	likely_pathogenic	0.5754	pathogenic	-0.299	Destabilizing	0.998	D	0.733	prob.delet.	None	None	None	None	N
K/I	0.9125	likely_pathogenic	0.8118	pathogenic	0.427	Stabilizing	0.991	D	0.807	deleterious	N	0.467747934	None	None	N
K/L	0.8537	likely_pathogenic	0.7541	pathogenic	0.427	Stabilizing	0.986	D	0.703	prob.neutral	None	None	None	None	N
K/M	0.7955	likely_pathogenic	0.6563	pathogenic	0.12	Stabilizing	0.999	D	0.722	prob.delet.	None	None	None	None	N
K/N	0.9463	likely_pathogenic	0.8888	pathogenic	0.176	Stabilizing	0.982	D	0.607	neutral	N	0.49098075	None	None	N
K/P	0.987	likely_pathogenic	0.9725	pathogenic	0.331	Stabilizing	0.998	D	0.766	deleterious	None	None	None	None	N
K/Q	0.504	ambiguous	0.3669	ambiguous	0.015	Stabilizing	0.982	D	0.591	neutral	N	0.513190412	None	None	N
K/R	0.1053	likely_benign	0.0933	benign	-0.009	Destabilizing	0.046	N	0.195	neutral	N	0.506571084	None	None	N
K/S	0.9034	likely_pathogenic	0.8207	pathogenic	-0.243	Destabilizing	0.953	D	0.549	neutral	None	None	None	None	N
K/T	0.6849	likely_pathogenic	0.5204	ambiguous	-0.108	Destabilizing	0.991	D	0.721	prob.delet.	N	0.454659397	None	None	N
K/V	0.8652	likely_pathogenic	0.7524	pathogenic	0.331	Stabilizing	0.993	D	0.77	deleterious	None	None	None	None	N
K/W	0.9569	likely_pathogenic	0.9285	pathogenic	-0.264	Destabilizing	0.999	D	0.769	deleterious	None	None	None	None	N
K/Y	0.9563	likely_pathogenic	0.9189	pathogenic	0.096	Stabilizing	0.998	D	0.791	deleterious	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.