TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8604	26035;26036;26037	chr2:178715604;178715603;178715602	chr2:179580331;179580330;179580329
N2AB	8287	25084;25085;25086	chr2:178715604;178715603;178715602	chr2:179580331;179580330;179580329
N2A	7360	22303;22304;22305	chr2:178715604;178715603;178715602	chr2:179580331;179580330;179580329
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: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-71
• Domain position: 56
• Structural Position: 135
• Q(SASA): 0.2746
• 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/A	None	None	0.954	N	0.498	0.323	0.644857554221	gnomAD-4.0.0	1.59158E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43283E-05	0
V/M	rs1160730554	-0.365	0.99	N	0.75	0.323	0.556850889111	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
V/M	rs1160730554	-0.365	0.99	N	0.75	0.323	0.556850889111	gnomAD-4.0.0	1.59157E-06	None	None	None	None	N	None	5.66059E-05	0	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
V/A	0.1891	likely_benign	0.1841	benign	-1.607	Destabilizing	0.954	D	0.498	neutral	N	0.491097606	None	None	N
V/C	0.8027	likely_pathogenic	0.791	pathogenic	-1.079	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
V/D	0.4691	ambiguous	0.4496	ambiguous	-1.568	Destabilizing	0.999	D	0.797	deleterious	None	None	None	None	N
V/E	0.264	likely_benign	0.2577	benign	-1.522	Destabilizing	0.994	D	0.768	deleterious	D	0.529496377	None	None	N
V/F	0.1628	likely_benign	0.164	benign	-1.13	Destabilizing	0.994	D	0.785	deleterious	None	None	None	None	N
V/G	0.3332	likely_benign	0.3179	benign	-1.97	Destabilizing	0.999	D	0.765	deleterious	N	0.506987664	None	None	N
V/H	0.5054	ambiguous	0.4916	ambiguous	-1.562	Destabilizing	1.0	D	0.764	deleterious	None	None	None	None	N
V/I	0.079	likely_benign	0.0753	benign	-0.686	Destabilizing	0.471	N	0.474	neutral	None	None	None	None	N
V/K	0.284	likely_benign	0.2793	benign	-1.276	Destabilizing	0.994	D	0.771	deleterious	None	None	None	None	N
V/L	0.165	likely_benign	0.169	benign	-0.686	Destabilizing	0.01	N	0.277	neutral	N	0.499002899	None	None	N
V/M	0.0834	likely_benign	0.0865	benign	-0.569	Destabilizing	0.99	D	0.75	deleterious	N	0.502088745	None	None	N
V/N	0.302	likely_benign	0.2923	benign	-1.148	Destabilizing	0.987	D	0.791	deleterious	None	None	None	None	N
V/P	0.9499	likely_pathogenic	0.9405	pathogenic	-0.96	Destabilizing	0.987	D	0.786	deleterious	None	None	None	None	N
V/Q	0.257	likely_benign	0.2582	benign	-1.265	Destabilizing	0.997	D	0.785	deleterious	None	None	None	None	N
V/R	0.2764	likely_benign	0.276	benign	-0.842	Destabilizing	0.997	D	0.789	deleterious	None	None	None	None	N
V/S	0.2232	likely_benign	0.2151	benign	-1.71	Destabilizing	0.995	D	0.753	deleterious	None	None	None	None	N
V/T	0.1343	likely_benign	0.1322	benign	-1.554	Destabilizing	0.958	D	0.569	neutral	None	None	None	None	N
V/W	0.7547	likely_pathogenic	0.733	pathogenic	-1.4	Destabilizing	1.0	D	0.766	deleterious	None	None	None	None	N
V/Y	0.5199	ambiguous	0.5106	ambiguous	-1.084	Destabilizing	0.997	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.