TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32208	96847;96848;96849	chr2:178543351;178543350;178543349	chr2:179408078;179408077;179408076
N2AB	30567	91924;91925;91926	chr2:178543351;178543350;178543349	chr2:179408078;179408077;179408076
N2A	29640	89143;89144;89145	chr2:178543351;178543350;178543349	chr2:179408078;179408077;179408076
N2B	23143	69652;69653;69654	chr2:178543351;178543350;178543349	chr2:179408078;179408077;179408076
Novex-1	23268	70027;70028;70029	chr2:178543351;178543350;178543349	chr2:179408078;179408077;179408076
Novex-2	23335	70228;70229;70230	chr2:178543351;178543350;178543349	chr2:179408078;179408077;179408076
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: Fn3-123
• Domain position: 7
• Structural Position: 7
• Q(SASA): 0.6264
• 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/R	None	None	0.887	N	0.532	0.139	0.245660935333	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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	0.3179	likely_benign	0.3091	benign	-0.011	Destabilizing	0.983	D	0.581	neutral	None	None	None	None	I
K/C	0.675	likely_pathogenic	0.6611	pathogenic	-0.167	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	I
K/D	0.5022	ambiguous	0.4846	ambiguous	-0.027	Destabilizing	0.035	N	0.279	neutral	None	None	None	None	I
K/E	0.2433	likely_benign	0.2439	benign	-0.02	Destabilizing	0.565	D	0.547	neutral	N	0.48074992	None	None	I
K/F	0.7719	likely_pathogenic	0.7459	pathogenic	-0.157	Destabilizing	0.996	D	0.708	prob.delet.	None	None	None	None	I
K/G	0.3658	ambiguous	0.3632	ambiguous	-0.228	Destabilizing	0.965	D	0.581	neutral	None	None	None	None	I
K/H	0.2723	likely_benign	0.2644	benign	-0.511	Destabilizing	0.999	D	0.631	neutral	None	None	None	None	I
K/I	0.4643	ambiguous	0.4548	ambiguous	0.485	Stabilizing	0.946	D	0.704	prob.neutral	None	None	None	None	I
K/L	0.4115	ambiguous	0.3953	ambiguous	0.485	Stabilizing	0.853	D	0.574	neutral	None	None	None	None	I
K/M	0.2945	likely_benign	0.2877	benign	0.29	Stabilizing	0.995	D	0.625	neutral	N	0.506917801	None	None	I
K/N	0.3746	ambiguous	0.3657	ambiguous	0.202	Stabilizing	0.954	D	0.533	neutral	N	0.389354337	None	None	I
K/P	0.7788	likely_pathogenic	0.7766	pathogenic	0.349	Stabilizing	0.998	D	0.6	neutral	None	None	None	None	I
K/Q	0.1542	likely_benign	0.1511	benign	0.007	Stabilizing	0.947	D	0.559	neutral	N	0.473207872	None	None	I
K/R	0.0793	likely_benign	0.0782	benign	-0.084	Destabilizing	0.887	D	0.532	neutral	N	0.47338123	None	None	I
K/S	0.3681	ambiguous	0.3454	ambiguous	-0.279	Destabilizing	0.965	D	0.539	neutral	None	None	None	None	I
K/T	0.1898	likely_benign	0.188	benign	-0.123	Destabilizing	0.927	D	0.58	neutral	N	0.466628616	None	None	I
K/V	0.3534	ambiguous	0.3455	ambiguous	0.349	Stabilizing	0.959	D	0.576	neutral	None	None	None	None	I
K/W	0.7911	likely_pathogenic	0.769	pathogenic	-0.152	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	I
K/Y	0.6311	likely_pathogenic	0.6106	pathogenic	0.185	Stabilizing	0.965	D	0.699	prob.neutral	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.