TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27954	84085;84086;84087	chr2:178562272;178562271;178562270	chr2:179426999;179426998;179426997
N2AB	26313	79162;79163;79164	chr2:178562272;178562271;178562270	chr2:179426999;179426998;179426997
N2A	25386	76381;76382;76383	chr2:178562272;178562271;178562270	chr2:179426999;179426998;179426997
N2B	18889	56890;56891;56892	chr2:178562272;178562271;178562270	chr2:179426999;179426998;179426997
Novex-1	19014	57265;57266;57267	chr2:178562272;178562271;178562270	chr2:179426999;179426998;179426997
Novex-2	19081	57466;57467;57468	chr2:178562272;178562271;178562270	chr2:179426999;179426998;179426997
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Fn3-91
• Domain position: 92
• Structural Position: 127
• Q(SASA): 0.2278
• 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
V/I	None	None	0.984	D	0.582	0.221	0.707817649444	gnomAD-4.0.0	6.84384E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99569E-07	0	0
V/L	rs1703951174	None	0.984	N	0.631	0.322	0.647688206944	gnomAD-4.0.0	6.84384E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99569E-07	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
V/A	0.6937	likely_pathogenic	0.7483	pathogenic	-1.698	Destabilizing	0.999	D	0.639	neutral	D	0.547385381	None	None	N
V/C	0.9434	likely_pathogenic	0.9512	pathogenic	-1.002	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
V/D	0.994	likely_pathogenic	0.9957	pathogenic	-2.589	Highly Destabilizing	1.0	D	0.898	deleterious	None	None	None	None	N
V/E	0.9745	likely_pathogenic	0.9802	pathogenic	-2.315	Highly Destabilizing	0.999	D	0.886	deleterious	D	0.547385381	None	None	N
V/F	0.6474	likely_pathogenic	0.7071	pathogenic	-1.073	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
V/G	0.8861	likely_pathogenic	0.9165	pathogenic	-2.226	Highly Destabilizing	1.0	D	0.889	deleterious	D	0.548906318	None	None	N
V/H	0.9896	likely_pathogenic	0.9918	pathogenic	-2.039	Highly Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
V/I	0.1023	likely_benign	0.1044	benign	-0.194	Destabilizing	0.984	D	0.582	neutral	D	0.527514865	None	None	N
V/K	0.9811	likely_pathogenic	0.9851	pathogenic	-1.41	Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
V/L	0.5829	likely_pathogenic	0.6043	pathogenic	-0.194	Destabilizing	0.984	D	0.631	neutral	N	0.504326789	None	None	N
V/M	0.5033	ambiguous	0.5365	ambiguous	-0.217	Destabilizing	1.0	D	0.659	prob.neutral	None	None	None	None	N
V/N	0.9752	likely_pathogenic	0.9817	pathogenic	-1.998	Destabilizing	0.998	D	0.91	deleterious	None	None	None	None	N
V/P	0.9913	likely_pathogenic	0.9927	pathogenic	-0.674	Destabilizing	0.998	D	0.885	deleterious	None	None	None	None	N
V/Q	0.9636	likely_pathogenic	0.971	pathogenic	-1.721	Destabilizing	1.0	D	0.896	deleterious	None	None	None	None	N
V/R	0.9685	likely_pathogenic	0.9755	pathogenic	-1.503	Destabilizing	1.0	D	0.913	deleterious	None	None	None	None	N
V/S	0.9024	likely_pathogenic	0.926	pathogenic	-2.487	Highly Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
V/T	0.7603	likely_pathogenic	0.782	pathogenic	-2.059	Highly Destabilizing	0.998	D	0.541	neutral	None	None	None	None	N
V/W	0.9935	likely_pathogenic	0.9952	pathogenic	-1.59	Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	N
V/Y	0.9626	likely_pathogenic	0.9712	pathogenic	-1.137	Destabilizing	1.0	D	0.796	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.