TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27822	83689;83690;83691	chr2:178562668;178562667;178562666	chr2:179427395;179427394;179427393
N2AB	26181	78766;78767;78768	chr2:178562668;178562667;178562666	chr2:179427395;179427394;179427393
N2A	25254	75985;75986;75987	chr2:178562668;178562667;178562666	chr2:179427395;179427394;179427393
N2B	18757	56494;56495;56496	chr2:178562668;178562667;178562666	chr2:179427395;179427394;179427393
Novex-1	18882	56869;56870;56871	chr2:178562668;178562667;178562666	chr2:179427395;179427394;179427393
Novex-2	18949	57070;57071;57072	chr2:178562668;178562667;178562666	chr2:179427395;179427394;179427393
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: Fn3-90
• Domain position: 57
• Structural Position: 88
• Q(SASA): 0.3975
• 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	rs1269206431	0.221	0.948	N	0.43	0.239	0.259272394797	gnomAD-2.1.1	4.3E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.27E-06	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	0.5727	likely_pathogenic	0.6373	pathogenic	-0.041	Destabilizing	0.988	D	0.441	neutral	None	None	None	None	N
K/C	0.8276	likely_pathogenic	0.862	pathogenic	-0.28	Destabilizing	1.0	D	0.634	neutral	None	None	None	None	N
K/D	0.7971	likely_pathogenic	0.8408	pathogenic	0.114	Stabilizing	0.998	D	0.499	neutral	None	None	None	None	N
K/E	0.5103	ambiguous	0.577	pathogenic	0.156	Stabilizing	0.948	D	0.43	neutral	N	0.472647725	None	None	N
K/F	0.947	likely_pathogenic	0.9613	pathogenic	-0.119	Destabilizing	0.999	D	0.603	neutral	None	None	None	None	N
K/G	0.5974	likely_pathogenic	0.6476	pathogenic	-0.278	Destabilizing	0.994	D	0.453	neutral	None	None	None	None	N
K/H	0.4577	ambiguous	0.5209	ambiguous	-0.491	Destabilizing	0.999	D	0.55	neutral	None	None	None	None	N
K/I	0.789	likely_pathogenic	0.8303	pathogenic	0.518	Stabilizing	0.975	D	0.599	neutral	N	0.472547327	None	None	N
K/L	0.7225	likely_pathogenic	0.7673	pathogenic	0.518	Stabilizing	0.704	D	0.453	neutral	None	None	None	None	N
K/M	0.61	likely_pathogenic	0.6671	pathogenic	0.136	Stabilizing	0.999	D	0.544	neutral	None	None	None	None	N
K/N	0.6991	likely_pathogenic	0.754	pathogenic	0.086	Stabilizing	0.998	D	0.446	neutral	N	0.505379006	None	None	N
K/P	0.9352	likely_pathogenic	0.9407	pathogenic	0.361	Stabilizing	0.999	D	0.546	neutral	None	None	None	None	N
K/Q	0.2615	likely_benign	0.3099	benign	0.006	Stabilizing	0.963	D	0.472	neutral	N	0.457739774	None	None	N
K/R	0.0823	likely_benign	0.0867	benign	-0.101	Destabilizing	0.015	N	0.133	neutral	N	0.414989075	None	None	N
K/S	0.6528	likely_pathogenic	0.7064	pathogenic	-0.394	Destabilizing	0.994	D	0.427	neutral	None	None	None	None	N
K/T	0.4555	ambiguous	0.5196	ambiguous	-0.186	Destabilizing	0.974	D	0.485	neutral	N	0.478957621	None	None	N
K/V	0.6871	likely_pathogenic	0.735	pathogenic	0.361	Stabilizing	0.957	D	0.495	neutral	None	None	None	None	N
K/W	0.9146	likely_pathogenic	0.9383	pathogenic	-0.152	Destabilizing	1.0	D	0.639	neutral	None	None	None	None	N
K/Y	0.8461	likely_pathogenic	0.8783	pathogenic	0.194	Stabilizing	0.988	D	0.587	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.