TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7087	21484;21485;21486	chr2:178724000;178723999;178723998	chr2:179588727;179588726;179588725
N2AB	6770	20533;20534;20535	chr2:178724000;178723999;178723998	chr2:179588727;179588726;179588725
N2A	5843	17752;17753;17754	chr2:178724000;178723999;178723998	chr2:179588727;179588726;179588725
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Ig-55
• Domain position: 44
• Structural Position: 73
• Q(SASA): 0.8216
• 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/R	rs1170087818	-0.078	0.999	N	0.747	0.385	0.615496883321	gnomAD-2.1.1	8.06E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	4.64E-05	0	0
G/R	rs1170087818	-0.078	0.999	N	0.747	0.385	0.615496883321	gnomAD-4.0.0	3.1838E-06	None	None	None	None	I	None	0	0	None	0	0	None	1.8826E-05	0	0	1.43295E-05	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	0.1808	likely_benign	0.1624	benign	-0.27	Destabilizing	0.998	D	0.461	neutral	N	0.47814169	None	None	I
G/C	0.3354	likely_benign	0.3568	ambiguous	-0.944	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	I
G/D	0.2057	likely_benign	0.2011	benign	-0.352	Destabilizing	0.504	D	0.42	neutral	None	None	None	None	I
G/E	0.2824	likely_benign	0.2849	benign	-0.508	Destabilizing	0.992	D	0.561	neutral	N	0.464872827	None	None	I
G/F	0.7307	likely_pathogenic	0.7334	pathogenic	-0.955	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	I
G/H	0.4692	ambiguous	0.4628	ambiguous	-0.412	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	I
G/I	0.5417	ambiguous	0.5594	ambiguous	-0.43	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	I
G/K	0.4954	ambiguous	0.5136	ambiguous	-0.681	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	I
G/L	0.5786	likely_pathogenic	0.5686	pathogenic	-0.43	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	I
G/M	0.6161	likely_pathogenic	0.6071	pathogenic	-0.538	Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	I
G/N	0.2787	likely_benign	0.2769	benign	-0.407	Destabilizing	0.999	D	0.653	neutral	None	None	None	None	I
G/P	0.9124	likely_pathogenic	0.9103	pathogenic	-0.345	Destabilizing	1.0	D	0.72	prob.delet.	None	None	None	None	I
G/Q	0.433	ambiguous	0.428	ambiguous	-0.662	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	I
G/R	0.351	ambiguous	0.3663	ambiguous	-0.268	Destabilizing	0.999	D	0.747	deleterious	N	0.479965342	None	None	I
G/S	0.0871	likely_benign	0.0793	benign	-0.587	Destabilizing	0.997	D	0.521	neutral	None	None	None	None	I
G/T	0.1699	likely_benign	0.1664	benign	-0.665	Destabilizing	1.0	D	0.698	prob.neutral	None	None	None	None	I
G/V	0.3525	ambiguous	0.3612	ambiguous	-0.345	Destabilizing	1.0	D	0.771	deleterious	N	0.493398789	None	None	I
G/W	0.5862	likely_pathogenic	0.5983	pathogenic	-1.085	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	I
G/Y	0.6148	likely_pathogenic	0.616	pathogenic	-0.744	Destabilizing	1.0	D	0.797	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.