TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32022	96289;96290;96291	chr2:178544080;178544079;178544078	chr2:179408807;179408806;179408805
N2AB	30381	91366;91367;91368	chr2:178544080;178544079;178544078	chr2:179408807;179408806;179408805
N2A	29454	88585;88586;88587	chr2:178544080;178544079;178544078	chr2:179408807;179408806;179408805
N2B	22957	69094;69095;69096	chr2:178544080;178544079;178544078	chr2:179408807;179408806;179408805
Novex-1	23082	69469;69470;69471	chr2:178544080;178544079;178544078	chr2:179408807;179408806;179408805
Novex-2	23149	69670;69671;69672	chr2:178544080;178544079;178544078	chr2:179408807;179408806;179408805
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-153
• Domain position: 6
• Structural Position: 9
• Q(SASA): 0.7657
• 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/Q	None	None	0.946	N	0.648	0.43	0.343560092441	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	6.17284E-04	0	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	0.7544	likely_pathogenic	0.7021	pathogenic	0.058	Stabilizing	0.87	D	0.591	neutral	None	None	None	None	N
K/C	0.9041	likely_pathogenic	0.888	pathogenic	-0.096	Destabilizing	0.998	D	0.718	prob.delet.	None	None	None	None	N
K/D	0.8036	likely_pathogenic	0.7457	pathogenic	0.069	Stabilizing	0.959	D	0.697	prob.neutral	None	None	None	None	N
K/E	0.5311	ambiguous	0.434	ambiguous	0.069	Stabilizing	0.716	D	0.568	neutral	N	0.512473628	None	None	N
K/F	0.9682	likely_pathogenic	0.9533	pathogenic	-0.174	Destabilizing	0.994	D	0.688	prob.neutral	None	None	None	None	N
K/G	0.7368	likely_pathogenic	0.6803	pathogenic	-0.134	Destabilizing	0.959	D	0.516	neutral	None	None	None	None	N
K/H	0.5589	ambiguous	0.4992	ambiguous	-0.424	Destabilizing	0.994	D	0.689	prob.neutral	None	None	None	None	N
K/I	0.8501	likely_pathogenic	0.801	pathogenic	0.482	Stabilizing	0.979	D	0.707	prob.neutral	None	None	None	None	N
K/L	0.7808	likely_pathogenic	0.7166	pathogenic	0.482	Stabilizing	0.959	D	0.516	neutral	None	None	None	None	N
K/M	0.653	likely_pathogenic	0.5462	ambiguous	0.293	Stabilizing	0.998	D	0.693	prob.neutral	D	0.523959344	None	None	N
K/N	0.6772	likely_pathogenic	0.5918	pathogenic	0.313	Stabilizing	0.946	D	0.657	neutral	D	0.535062486	None	None	N
K/P	0.9361	likely_pathogenic	0.9195	pathogenic	0.368	Stabilizing	0.979	D	0.705	prob.neutral	None	None	None	None	N
K/Q	0.2845	likely_benign	0.2376	benign	0.132	Stabilizing	0.946	D	0.648	neutral	N	0.512473628	None	None	N
K/R	0.1124	likely_benign	0.1057	benign	-0.003	Destabilizing	0.035	N	0.302	neutral	N	0.47737962	None	None	N
K/S	0.7685	likely_pathogenic	0.7056	pathogenic	-0.156	Destabilizing	0.87	D	0.601	neutral	None	None	None	None	N
K/T	0.5527	ambiguous	0.4755	ambiguous	-0.013	Destabilizing	0.946	D	0.639	neutral	N	0.487786833	None	None	N
K/V	0.7845	likely_pathogenic	0.7324	pathogenic	0.368	Stabilizing	0.959	D	0.646	neutral	None	None	None	None	N
K/W	0.9481	likely_pathogenic	0.9278	pathogenic	-0.207	Destabilizing	0.998	D	0.723	prob.delet.	None	None	None	None	N
K/Y	0.8765	likely_pathogenic	0.8298	pathogenic	0.153	Stabilizing	0.979	D	0.67	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.