TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26430	79513;79514;79515	chr2:178566844;178566843;178566842	chr2:179431571;179431570;179431569
N2AB	24789	74590;74591;74592	chr2:178566844;178566843;178566842	chr2:179431571;179431570;179431569
N2A	23862	71809;71810;71811	chr2:178566844;178566843;178566842	chr2:179431571;179431570;179431569
N2B	17365	52318;52319;52320	chr2:178566844;178566843;178566842	chr2:179431571;179431570;179431569
Novex-1	17490	52693;52694;52695	chr2:178566844;178566843;178566842	chr2:179431571;179431570;179431569
Novex-2	17557	52894;52895;52896	chr2:178566844;178566843;178566842	chr2:179431571;179431570;179431569
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Fn3-80
• Domain position: 45
• Structural Position: 60
• Q(SASA): 0.2583
• 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
G/A	None	None	0.45	N	0.505	0.337	0.256283259241	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31252E-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
G/A	0.3968	ambiguous	0.2906	benign	-0.295	Destabilizing	0.45	N	0.505	neutral	N	0.474074128	None	None	N
G/C	0.6716	likely_pathogenic	0.5635	ambiguous	-0.889	Destabilizing	1.0	D	0.778	deleterious	N	0.513702906	None	None	N
G/D	0.9468	likely_pathogenic	0.9284	pathogenic	-0.504	Destabilizing	0.999	D	0.72	prob.delet.	N	0.512030045	None	None	N
G/E	0.9548	likely_pathogenic	0.93	pathogenic	-0.668	Destabilizing	0.998	D	0.724	prob.delet.	None	None	None	None	N
G/F	0.9705	likely_pathogenic	0.9502	pathogenic	-1.005	Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
G/H	0.9395	likely_pathogenic	0.9224	pathogenic	-0.504	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
G/I	0.9065	likely_pathogenic	0.8487	pathogenic	-0.45	Destabilizing	0.999	D	0.795	deleterious	None	None	None	None	N
G/K	0.9816	likely_pathogenic	0.9751	pathogenic	-0.799	Destabilizing	0.998	D	0.724	prob.delet.	None	None	None	None	N
G/L	0.9156	likely_pathogenic	0.8651	pathogenic	-0.45	Destabilizing	0.996	D	0.742	deleterious	None	None	None	None	N
G/M	0.9286	likely_pathogenic	0.8791	pathogenic	-0.501	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
G/N	0.8237	likely_pathogenic	0.7568	pathogenic	-0.442	Destabilizing	0.999	D	0.728	prob.delet.	None	None	None	None	N
G/P	0.9954	likely_pathogenic	0.9932	pathogenic	-0.366	Destabilizing	0.999	D	0.767	deleterious	None	None	None	None	N
G/Q	0.9291	likely_pathogenic	0.8986	pathogenic	-0.727	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
G/R	0.9423	likely_pathogenic	0.925	pathogenic	-0.352	Destabilizing	0.999	D	0.782	deleterious	N	0.47571997	None	None	N
G/S	0.229	likely_benign	0.1691	benign	-0.598	Destabilizing	0.995	D	0.653	neutral	N	0.451730948	None	None	N
G/T	0.6217	likely_pathogenic	0.5078	ambiguous	-0.692	Destabilizing	0.998	D	0.709	prob.delet.	None	None	None	None	N
G/V	0.7998	likely_pathogenic	0.698	pathogenic	-0.366	Destabilizing	0.995	D	0.738	prob.delet.	N	0.481520094	None	None	N
G/W	0.9504	likely_pathogenic	0.9319	pathogenic	-1.144	Destabilizing	1.0	D	0.776	deleterious	None	None	None	None	N
G/Y	0.9567	likely_pathogenic	0.9352	pathogenic	-0.806	Destabilizing	1.0	D	0.793	deleterious	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.