TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7154	21685;21686;21687	chr2:178723640;178723639;178723638	chr2:179588367;179588366;179588365
N2AB	6837	20734;20735;20736	chr2:178723640;178723639;178723638	chr2:179588367;179588366;179588365
N2A	5910	17953;17954;17955	chr2:178723640;178723639;178723638	chr2:179588367;179588366;179588365
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: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Ig-56
• Domain position: 18
• Structural Position: 28
• Q(SASA): 0.0998
• 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	0.001	N	0.214	0.06	0.270889551736	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
V/A	0.2543	likely_benign	0.2681	benign	-1.697	Destabilizing	0.001	N	0.335	neutral	N	0.515142134	None	None	N
V/C	0.7817	likely_pathogenic	0.7749	pathogenic	-1.488	Destabilizing	0.909	D	0.74	deleterious	None	None	None	None	N
V/D	0.7748	likely_pathogenic	0.801	pathogenic	-1.446	Destabilizing	0.726	D	0.84	deleterious	None	None	None	None	N
V/E	0.6557	likely_pathogenic	0.6906	pathogenic	-1.29	Destabilizing	0.497	N	0.821	deleterious	D	0.534054752	None	None	N
V/F	0.2962	likely_benign	0.2877	benign	-0.998	Destabilizing	0.567	D	0.823	deleterious	None	None	None	None	N
V/G	0.4598	ambiguous	0.4856	ambiguous	-2.148	Highly Destabilizing	0.331	N	0.818	deleterious	N	0.504594191	None	None	N
V/H	0.8482	likely_pathogenic	0.8555	pathogenic	-1.482	Destabilizing	0.968	D	0.808	deleterious	None	None	None	None	N
V/I	0.0813	likely_benign	0.0788	benign	-0.488	Destabilizing	0.001	N	0.214	neutral	N	0.507101441	None	None	N
V/K	0.6944	likely_pathogenic	0.7226	pathogenic	-1.443	Destabilizing	0.567	D	0.821	deleterious	None	None	None	None	N
V/L	0.2442	likely_benign	0.2379	benign	-0.488	Destabilizing	0.02	N	0.499	neutral	N	0.459846397	None	None	N
V/M	0.1842	likely_benign	0.1872	benign	-0.658	Destabilizing	0.567	D	0.66	neutral	None	None	None	None	N
V/N	0.6498	likely_pathogenic	0.6708	pathogenic	-1.645	Destabilizing	0.726	D	0.841	deleterious	None	None	None	None	N
V/P	0.952	likely_pathogenic	0.9544	pathogenic	-0.86	Destabilizing	0.726	D	0.81	deleterious	None	None	None	None	N
V/Q	0.6626	likely_pathogenic	0.6949	pathogenic	-1.539	Destabilizing	0.726	D	0.809	deleterious	None	None	None	None	N
V/R	0.6209	likely_pathogenic	0.644	pathogenic	-1.193	Destabilizing	0.726	D	0.837	deleterious	None	None	None	None	N
V/S	0.4649	ambiguous	0.4999	ambiguous	-2.312	Highly Destabilizing	0.396	N	0.804	deleterious	None	None	None	None	N
V/T	0.3218	likely_benign	0.3358	benign	-1.996	Destabilizing	0.272	N	0.646	neutral	None	None	None	None	N
V/W	0.9149	likely_pathogenic	0.9185	pathogenic	-1.236	Destabilizing	0.968	D	0.769	deleterious	None	None	None	None	N
V/Y	0.7162	likely_pathogenic	0.7217	pathogenic	-0.912	Destabilizing	0.726	D	0.788	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.