TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32780	98563;98564;98565	chr2:178539727;178539726;178539725	chr2:179404454;179404453;179404452
N2AB	31139	93640;93641;93642	chr2:178539727;178539726;178539725	chr2:179404454;179404453;179404452
N2A	30212	90859;90860;90861	chr2:178539727;178539726;178539725	chr2:179404454;179404453;179404452
N2B	23715	71368;71369;71370	chr2:178539727;178539726;178539725	chr2:179404454;179404453;179404452
Novex-1	23840	71743;71744;71745	chr2:178539727;178539726;178539725	chr2:179404454;179404453;179404452
Novex-2	23907	71944;71945;71946	chr2:178539727;178539726;178539725	chr2:179404454;179404453;179404452
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-155
• Domain position: 73
• Structural Position: 162
• Q(SASA): 0.9274
• 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	rs755409666	None	0.999	N	0.562	0.414	0.294918367191	gnomAD-4.0.0	3.42099E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	4.49729E-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	0.5798	likely_pathogenic	0.6071	pathogenic	0.039	Stabilizing	0.999	D	0.576	neutral	None	None	None	None	I
K/C	0.8669	likely_pathogenic	0.8815	pathogenic	-0.234	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	I
K/D	0.8175	likely_pathogenic	0.8265	pathogenic	-0.164	Destabilizing	1.0	D	0.634	neutral	None	None	None	None	I
K/E	0.535	ambiguous	0.5382	ambiguous	-0.178	Destabilizing	0.999	D	0.562	neutral	N	0.415634941	None	None	I
K/F	0.9434	likely_pathogenic	0.9517	pathogenic	-0.292	Destabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	I
K/G	0.7253	likely_pathogenic	0.7647	pathogenic	-0.107	Destabilizing	1.0	D	0.607	neutral	None	None	None	None	I
K/H	0.5452	ambiguous	0.571	pathogenic	-0.312	Destabilizing	1.0	D	0.651	neutral	None	None	None	None	I
K/I	0.595	likely_pathogenic	0.6167	pathogenic	0.337	Stabilizing	1.0	D	0.726	prob.delet.	N	0.466066548	None	None	I
K/L	0.6426	likely_pathogenic	0.6628	pathogenic	0.337	Stabilizing	1.0	D	0.607	neutral	None	None	None	None	I
K/M	0.567	likely_pathogenic	0.5867	pathogenic	0.084	Stabilizing	1.0	D	0.649	neutral	None	None	None	None	I
K/N	0.7216	likely_pathogenic	0.7282	pathogenic	0.211	Stabilizing	1.0	D	0.675	neutral	N	0.462314167	None	None	I
K/P	0.6302	likely_pathogenic	0.6573	pathogenic	0.262	Stabilizing	1.0	D	0.627	neutral	None	None	None	None	I
K/Q	0.3134	likely_benign	0.3256	benign	0.041	Stabilizing	1.0	D	0.671	neutral	N	0.475339392	None	None	I
K/R	0.1075	likely_benign	0.1095	benign	-0.018	Destabilizing	0.999	D	0.53	neutral	N	0.468797422	None	None	I
K/S	0.6741	likely_pathogenic	0.6927	pathogenic	-0.183	Destabilizing	0.999	D	0.597	neutral	None	None	None	None	I
K/T	0.3961	ambiguous	0.4161	ambiguous	-0.072	Destabilizing	1.0	D	0.609	neutral	N	0.47102965	None	None	I
K/V	0.5579	ambiguous	0.5811	pathogenic	0.262	Stabilizing	1.0	D	0.672	neutral	None	None	None	None	I
K/W	0.9383	likely_pathogenic	0.9481	pathogenic	-0.372	Destabilizing	1.0	D	0.776	deleterious	None	None	None	None	I
K/Y	0.8443	likely_pathogenic	0.8613	pathogenic	-0.011	Destabilizing	1.0	D	0.703	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.