TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32812	98659;98660;98661	chr2:178539631;178539630;178539629	chr2:179404358;179404357;179404356
N2AB	31171	93736;93737;93738	chr2:178539631;178539630;178539629	chr2:179404358;179404357;179404356
N2A	30244	90955;90956;90957	chr2:178539631;178539630;178539629	chr2:179404358;179404357;179404356
N2B	23747	71464;71465;71466	chr2:178539631;178539630;178539629	chr2:179404358;179404357;179404356
Novex-1	23872	71839;71840;71841	chr2:178539631;178539630;178539629	chr2:179404358;179404357;179404356
Novex-2	23939	72040;72041;72042	chr2:178539631;178539630;178539629	chr2:179404358;179404357;179404356
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Fn3-127
• Domain position: 18
• Structural Position: 19
• Q(SASA): 0.1529
• 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
S/P	None	None	0.999	D	0.773	0.541	0.477685322099	gnomAD-4.0.0	8.40225E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.18751E-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
S/A	0.1834	likely_benign	0.1628	benign	-0.911	Destabilizing	0.987	D	0.441	neutral	N	0.483710411	None	None	N
S/C	0.2578	likely_benign	0.2278	benign	-1.029	Destabilizing	1.0	D	0.736	prob.delet.	N	0.496271712	None	None	N
S/D	0.892	likely_pathogenic	0.8635	pathogenic	-1.86	Destabilizing	1.0	D	0.589	neutral	None	None	None	None	N
S/E	0.8725	likely_pathogenic	0.855	pathogenic	-1.725	Destabilizing	0.999	D	0.528	neutral	None	None	None	None	N
S/F	0.6699	likely_pathogenic	0.5959	pathogenic	-0.767	Destabilizing	0.997	D	0.775	deleterious	N	0.501284915	None	None	N
S/G	0.289	likely_benign	0.2429	benign	-1.228	Destabilizing	0.999	D	0.447	neutral	None	None	None	None	N
S/H	0.7145	likely_pathogenic	0.6714	pathogenic	-1.532	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
S/I	0.7575	likely_pathogenic	0.6993	pathogenic	-0.131	Destabilizing	0.995	D	0.724	prob.delet.	None	None	None	None	N
S/K	0.9681	likely_pathogenic	0.9538	pathogenic	-0.795	Destabilizing	0.999	D	0.525	neutral	None	None	None	None	N
S/L	0.4498	ambiguous	0.3753	ambiguous	-0.131	Destabilizing	0.269	N	0.481	neutral	None	None	None	None	N
S/M	0.5259	ambiguous	0.4749	ambiguous	-0.213	Destabilizing	0.998	D	0.764	deleterious	None	None	None	None	N
S/N	0.4763	ambiguous	0.4067	ambiguous	-1.32	Destabilizing	1.0	D	0.571	neutral	None	None	None	None	N
S/P	0.9937	likely_pathogenic	0.9904	pathogenic	-0.359	Destabilizing	0.999	D	0.773	deleterious	D	0.543583038	None	None	N
S/Q	0.8245	likely_pathogenic	0.7972	pathogenic	-1.254	Destabilizing	1.0	D	0.645	neutral	None	None	None	None	N
S/R	0.9418	likely_pathogenic	0.922	pathogenic	-0.889	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
S/T	0.189	likely_benign	0.1648	benign	-1.02	Destabilizing	0.994	D	0.468	neutral	N	0.506133941	None	None	N
S/V	0.6621	likely_pathogenic	0.6003	pathogenic	-0.359	Destabilizing	0.983	D	0.674	neutral	None	None	None	None	N
S/W	0.7547	likely_pathogenic	0.7078	pathogenic	-0.982	Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	N
S/Y	0.5474	ambiguous	0.4818	ambiguous	-0.592	Destabilizing	0.999	D	0.785	deleterious	N	0.520508747	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.