TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23268	70027;70028;70029	chr2:178576330;178576329;178576328	chr2:179441057;179441056;179441055
N2AB	21627	65104;65105;65106	chr2:178576330;178576329;178576328	chr2:179441057;179441056;179441055
N2A	20700	62323;62324;62325	chr2:178576330;178576329;178576328	chr2:179441057;179441056;179441055
N2B	14203	42832;42833;42834	chr2:178576330;178576329;178576328	chr2:179441057;179441056;179441055
Novex-1	14328	43207;43208;43209	chr2:178576330;178576329;178576328	chr2:179441057;179441056;179441055
Novex-2	14395	43408;43409;43410	chr2:178576330;178576329;178576328	chr2:179441057;179441056;179441055
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGT
• RefSeq wild type template codon: CCA
• Domain: Fn3-57
• Domain position: 29
• Structural Position: 31
• Q(SASA): 0.2555
• 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
G/V	rs1201998813	-0.557	1.0	D	0.81	0.652	0.5813134048	gnomAD-2.1.1	4.87E-06	None	None	None	None	I	None	0	3.75E-05	None	0	0	None	0	None	0	0	0
G/V	rs1201998813	-0.557	1.0	D	0.81	0.652	0.5813134048	gnomAD-4.0.0	1.71243E-06	None	None	None	None	I	None	0	2.82773E-05	None	0	0	None	0	0	0	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	0.9643	likely_pathogenic	0.9521	pathogenic	-0.423	Destabilizing	1.0	D	0.725	prob.delet.	D	0.52714958	None	None	I
G/C	0.9861	likely_pathogenic	0.9844	pathogenic	-0.649	Destabilizing	1.0	D	0.785	deleterious	D	0.539773333	None	None	I
G/D	0.9956	likely_pathogenic	0.995	pathogenic	-0.616	Destabilizing	1.0	D	0.841	deleterious	N	0.503511917	None	None	I
G/E	0.9973	likely_pathogenic	0.9969	pathogenic	-0.737	Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	I
G/F	0.9986	likely_pathogenic	0.9986	pathogenic	-0.933	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	I
G/H	0.9979	likely_pathogenic	0.9975	pathogenic	-0.834	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	I
G/I	0.9987	likely_pathogenic	0.9984	pathogenic	-0.32	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	I
G/K	0.9974	likely_pathogenic	0.997	pathogenic	-0.968	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	I
G/L	0.998	likely_pathogenic	0.9979	pathogenic	-0.32	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	I
G/M	0.999	likely_pathogenic	0.9989	pathogenic	-0.301	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	I
G/N	0.9948	likely_pathogenic	0.9953	pathogenic	-0.509	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	I
G/P	0.9997	likely_pathogenic	0.9995	pathogenic	-0.316	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	I
G/Q	0.997	likely_pathogenic	0.9967	pathogenic	-0.752	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	I
G/R	0.9889	likely_pathogenic	0.986	pathogenic	-0.56	Destabilizing	1.0	D	0.831	deleterious	N	0.501954981	None	None	I
G/S	0.944	likely_pathogenic	0.9244	pathogenic	-0.709	Destabilizing	1.0	D	0.798	deleterious	N	0.508031367	None	None	I
G/T	0.9948	likely_pathogenic	0.9932	pathogenic	-0.757	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	I
G/V	0.9969	likely_pathogenic	0.996	pathogenic	-0.316	Destabilizing	1.0	D	0.81	deleterious	D	0.528163538	None	None	I
G/W	0.9959	likely_pathogenic	0.9955	pathogenic	-1.188	Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	I
G/Y	0.9979	likely_pathogenic	0.9974	pathogenic	-0.809	Destabilizing	1.0	D	0.779	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.