TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4868	14827;14828;14829	chr2:178735844;178735843;178735842	chr2:179600571;179600570;179600569
N2AB	4551	13876;13877;13878	chr2:178735844;178735843;178735842	chr2:179600571;179600570;179600569
N2A	3624	11095;11096;11097	chr2:178735844;178735843;178735842	chr2:179600571;179600570;179600569
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: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-31
• Domain position: 74
• Structural Position: 157
• Q(SASA): 0.2516
• Predicted PPI site: I

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	rs1276077770	-0.392	0.939	N	0.587	0.366	0.39724302092	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
K/E	rs1276077770	-0.392	0.939	N	0.587	0.366	0.39724302092	gnomAD-4.0.0	1.5913E-06	None	None	None	None	I	None	0	2.28686E-05	None	0	0	None	0	0	0	0	0
K/R	None	None	0.1	N	0.383	0.118	0.245101548738	gnomAD-4.0.0	2.40067E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.62503E-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	0.7596	likely_pathogenic	0.6906	pathogenic	-0.676	Destabilizing	0.953	D	0.648	neutral	None	None	None	None	I
K/C	0.903	likely_pathogenic	0.869	pathogenic	-0.811	Destabilizing	0.999	D	0.743	deleterious	None	None	None	None	I
K/D	0.9609	likely_pathogenic	0.9357	pathogenic	-0.095	Destabilizing	0.993	D	0.762	deleterious	None	None	None	None	I
K/E	0.4836	ambiguous	0.3968	ambiguous	0.01	Stabilizing	0.939	D	0.587	neutral	N	0.435242831	None	None	I
K/F	0.9311	likely_pathogenic	0.9069	pathogenic	-0.459	Destabilizing	0.986	D	0.782	deleterious	None	None	None	None	I
K/G	0.9038	likely_pathogenic	0.8584	pathogenic	-1.028	Destabilizing	0.993	D	0.76	deleterious	None	None	None	None	I
K/H	0.6035	likely_pathogenic	0.5329	ambiguous	-1.347	Destabilizing	0.999	D	0.73	prob.delet.	None	None	None	None	I
K/I	0.5525	ambiguous	0.5068	ambiguous	0.227	Stabilizing	0.973	D	0.785	deleterious	None	None	None	None	I
K/L	0.6071	likely_pathogenic	0.5604	ambiguous	0.227	Stabilizing	0.778	D	0.691	prob.neutral	None	None	None	None	I
K/M	0.3915	ambiguous	0.3622	ambiguous	0.132	Stabilizing	0.76	D	0.559	neutral	N	0.403262519	None	None	I
K/N	0.868	likely_pathogenic	0.8205	pathogenic	-0.459	Destabilizing	0.991	D	0.656	neutral	N	0.480294365	None	None	I
K/P	0.9916	likely_pathogenic	0.9878	pathogenic	-0.044	Destabilizing	0.998	D	0.766	deleterious	None	None	None	None	I
K/Q	0.2766	likely_benign	0.2281	benign	-0.596	Destabilizing	0.982	D	0.675	neutral	N	0.459468622	None	None	I
K/R	0.1203	likely_benign	0.1037	benign	-0.539	Destabilizing	0.1	N	0.383	neutral	N	0.423968671	None	None	I
K/S	0.8155	likely_pathogenic	0.7497	pathogenic	-1.199	Destabilizing	0.953	D	0.613	neutral	None	None	None	None	I
K/T	0.4287	ambiguous	0.3496	ambiguous	-0.886	Destabilizing	0.982	D	0.732	prob.delet.	N	0.350698899	None	None	I
K/V	0.5317	ambiguous	0.4756	ambiguous	-0.044	Destabilizing	0.91	D	0.74	deleterious	None	None	None	None	I
K/W	0.9349	likely_pathogenic	0.9138	pathogenic	-0.279	Destabilizing	0.999	D	0.717	prob.delet.	None	None	None	None	I
K/Y	0.8587	likely_pathogenic	0.8268	pathogenic	0.033	Stabilizing	0.993	D	0.791	deleterious	None	None	None	None	I

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.