TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6492	19699;19700;19701	chr2:178728350;178728349;178728348	chr2:179593077;179593076;179593075
N2AB	6175	18748;18749;18750	chr2:178728350;178728349;178728348	chr2:179593077;179593076;179593075
N2A	5248	15967;15968;15969	chr2:178728350;178728349;178728348	chr2:179593077;179593076;179593075
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-49
• Domain position: 12
• Structural Position: 16
• Q(SASA): 0.178
• 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	rs781106189	-0.366	0.012	N	0.095	0.219	0.247872288689	gnomAD-2.1.1	1.26E-05	None	None	None	None	N	None	0	0	None	0	0	None	1.04471E-04	None	0	0	0
K/E	rs781106189	-0.366	0.012	N	0.095	0.219	0.247872288689	gnomAD-4.0.0	1.03148E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.70469E-06	1.18092E-04	3.33233E-05

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	0.1933	likely_benign	0.2185	benign	-0.771	Destabilizing	0.373	N	0.363	neutral	None	None	None	None	N
K/C	0.5649	likely_pathogenic	0.6585	pathogenic	-0.843	Destabilizing	0.996	D	0.505	neutral	None	None	None	None	N
K/D	0.447	ambiguous	0.5032	ambiguous	-0.061	Destabilizing	0.59	D	0.365	neutral	None	None	None	None	N
K/E	0.1179	likely_benign	0.1262	benign	0.105	Stabilizing	0.012	N	0.095	neutral	N	0.455270764	None	None	N
K/F	0.7078	likely_pathogenic	0.7801	pathogenic	-0.348	Destabilizing	0.953	D	0.535	neutral	None	None	None	None	N
K/G	0.3144	likely_benign	0.379	ambiguous	-1.177	Destabilizing	0.742	D	0.427	neutral	None	None	None	None	N
K/H	0.2679	likely_benign	0.3114	benign	-1.374	Destabilizing	0.984	D	0.445	neutral	None	None	None	None	N
K/I	0.2751	likely_benign	0.3203	benign	0.302	Stabilizing	0.028	N	0.305	neutral	N	0.428177376	None	None	N
K/L	0.3006	likely_benign	0.3535	ambiguous	0.302	Stabilizing	0.373	N	0.349	neutral	None	None	None	None	N
K/M	0.1649	likely_benign	0.1852	benign	0.054	Stabilizing	0.953	D	0.446	neutral	None	None	None	None	N
K/N	0.2972	likely_benign	0.3624	ambiguous	-0.657	Destabilizing	0.684	D	0.429	neutral	N	0.484630879	None	None	N
K/P	0.7893	likely_pathogenic	0.8201	pathogenic	-0.026	Destabilizing	0.953	D	0.467	neutral	None	None	None	None	N
K/Q	0.1108	likely_benign	0.118	benign	-0.593	Destabilizing	0.684	D	0.469	neutral	N	0.442610898	None	None	N
K/R	0.0847	likely_benign	0.092	benign	-0.624	Destabilizing	0.684	D	0.408	neutral	N	0.444053693	None	None	N
K/S	0.2547	likely_benign	0.3111	benign	-1.389	Destabilizing	0.373	N	0.379	neutral	None	None	None	None	N
K/T	0.1035	likely_benign	0.115	benign	-0.984	Destabilizing	0.003	N	0.133	neutral	N	0.427564088	None	None	N
K/V	0.229	likely_benign	0.2584	benign	-0.026	Destabilizing	0.373	N	0.349	neutral	None	None	None	None	N
K/W	0.7518	likely_pathogenic	0.8035	pathogenic	-0.211	Destabilizing	0.996	D	0.547	neutral	None	None	None	None	N
K/Y	0.523	ambiguous	0.5938	pathogenic	0.079	Stabilizing	0.984	D	0.495	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.