TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7623	23092;23093;23094	chr2:178721152;178721151;178721150	chr2:179585879;179585878;179585877
N2AB	7306	22141;22142;22143	chr2:178721152;178721151;178721150	chr2:179585879;179585878;179585877
N2A	6379	19360;19361;19362	chr2:178721152;178721151;178721150	chr2:179585879;179585878;179585877
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-61
• Domain position: 16
• Structural Position: 24
• Q(SASA): 0.2639
• 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/E	rs752804619	None	0.896	D	0.723	0.561	None	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	0	3.85356E-04	None	0	0	0	0	0
G/E	rs752804619	None	0.896	D	0.723	0.561	None	gnomAD-4.0.0	3.10661E-06	None	None	None	None	N	None	0	0	None	3.3873E-05	6.69733E-05	None	0	0	8.49909E-07	0	0
G/R	rs2078297932	None	0.059	D	0.517	0.678	0.649612440629	gnomAD-4.0.0	1.60242E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43972E-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	0.351	ambiguous	0.3304	benign	-0.389	Destabilizing	0.64	D	0.557	neutral	D	0.647274597	None	None	N
G/C	0.5666	likely_pathogenic	0.5733	pathogenic	-0.889	Destabilizing	0.999	D	0.783	deleterious	None	None	None	None	N
G/D	0.2487	likely_benign	0.2465	benign	-0.728	Destabilizing	0.976	D	0.713	prob.delet.	None	None	None	None	N
G/E	0.3267	likely_benign	0.3225	benign	-0.898	Destabilizing	0.896	D	0.723	prob.delet.	D	0.604304494	None	None	N
G/F	0.7818	likely_pathogenic	0.7902	pathogenic	-1.148	Destabilizing	0.996	D	0.776	deleterious	None	None	None	None	N
G/H	0.5085	ambiguous	0.5302	ambiguous	-0.62	Destabilizing	0.997	D	0.764	deleterious	None	None	None	None	N
G/I	0.8117	likely_pathogenic	0.815	pathogenic	-0.54	Destabilizing	0.988	D	0.771	deleterious	None	None	None	None	N
G/K	0.5155	ambiguous	0.5578	ambiguous	-0.818	Destabilizing	0.132	N	0.49	neutral	None	None	None	None	N
G/L	0.7265	likely_pathogenic	0.7136	pathogenic	-0.54	Destabilizing	0.976	D	0.76	deleterious	None	None	None	None	N
G/M	0.7438	likely_pathogenic	0.7422	pathogenic	-0.444	Destabilizing	0.999	D	0.783	deleterious	None	None	None	None	N
G/N	0.3361	likely_benign	0.3243	benign	-0.476	Destabilizing	0.919	D	0.623	neutral	None	None	None	None	N
G/P	0.9782	likely_pathogenic	0.9782	pathogenic	-0.457	Destabilizing	0.988	D	0.746	deleterious	None	None	None	None	N
G/Q	0.4485	ambiguous	0.4579	ambiguous	-0.814	Destabilizing	0.976	D	0.748	deleterious	None	None	None	None	N
G/R	0.4236	ambiguous	0.4473	ambiguous	-0.341	Destabilizing	0.059	N	0.517	neutral	D	0.626117253	None	None	N
G/S	0.2016	likely_benign	0.1891	benign	-0.611	Destabilizing	0.307	N	0.322	neutral	None	None	None	None	N
G/T	0.4297	ambiguous	0.4202	ambiguous	-0.72	Destabilizing	0.851	D	0.738	prob.delet.	None	None	None	None	N
G/V	0.6719	likely_pathogenic	0.6602	pathogenic	-0.457	Destabilizing	0.984	D	0.759	deleterious	D	0.647678205	None	None	N
G/W	0.5833	likely_pathogenic	0.6074	pathogenic	-1.268	Destabilizing	0.999	D	0.753	deleterious	None	None	None	None	N
G/Y	0.6237	likely_pathogenic	0.6399	pathogenic	-0.927	Destabilizing	0.996	D	0.776	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.