TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27641	83146;83147;83148	chr2:178563211;178563210;178563209	chr2:179427938;179427937;179427936
N2AB	26000	78223;78224;78225	chr2:178563211;178563210;178563209	chr2:179427938;179427937;179427936
N2A	25073	75442;75443;75444	chr2:178563211;178563210;178563209	chr2:179427938;179427937;179427936
N2B	18576	55951;55952;55953	chr2:178563211;178563210;178563209	chr2:179427938;179427937;179427936
Novex-1	18701	56326;56327;56328	chr2:178563211;178563210;178563209	chr2:179427938;179427937;179427936
Novex-2	18768	56527;56528;56529	chr2:178563211;178563210;178563209	chr2:179427938;179427937;179427936
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-89
• Domain position: 72
• Structural Position: 103
• Q(SASA): 0.4454
• 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
E/K	None	None	0.999	N	0.589	0.389	0.354396617058	gnomAD-4.0.0	6.84252E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.65684E-05
E/Q	None	None	1.0	N	0.614	0.395	0.273938319068	gnomAD-4.0.0	2.05276E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69857E-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
E/A	0.1024	likely_benign	0.0978	benign	-1.127	Destabilizing	0.999	D	0.697	prob.neutral	N	0.47257378	None	None	N
E/C	0.7771	likely_pathogenic	0.7661	pathogenic	-0.464	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
E/D	0.1922	likely_benign	0.1942	benign	-0.987	Destabilizing	0.999	D	0.462	neutral	N	0.477168909	None	None	N
E/F	0.7436	likely_pathogenic	0.7221	pathogenic	-0.698	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
E/G	0.1885	likely_benign	0.1666	benign	-1.46	Destabilizing	1.0	D	0.758	deleterious	N	0.495553107	None	None	N
E/H	0.4368	ambiguous	0.4216	ambiguous	-0.905	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	N
E/I	0.2836	likely_benign	0.2722	benign	-0.217	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
E/K	0.1338	likely_benign	0.1255	benign	-0.496	Destabilizing	0.999	D	0.589	neutral	N	0.50764852	None	None	N
E/L	0.3316	likely_benign	0.3113	benign	-0.217	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
E/M	0.3753	ambiguous	0.3582	ambiguous	0.315	Stabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
E/N	0.2564	likely_benign	0.2569	benign	-0.953	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
E/P	0.3457	ambiguous	0.3373	benign	-0.5	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
E/Q	0.1166	likely_benign	0.1103	benign	-0.861	Destabilizing	1.0	D	0.614	neutral	N	0.475674425	None	None	N
E/R	0.2416	likely_benign	0.2248	benign	-0.27	Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	N
E/S	0.1699	likely_benign	0.166	benign	-1.269	Destabilizing	0.999	D	0.641	neutral	None	None	None	None	N
E/T	0.1551	likely_benign	0.1611	benign	-0.984	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
E/V	0.1582	likely_benign	0.1516	benign	-0.5	Destabilizing	1.0	D	0.799	deleterious	N	0.479183599	None	None	N
E/W	0.9209	likely_pathogenic	0.9031	pathogenic	-0.397	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
E/Y	0.6467	likely_pathogenic	0.622	pathogenic	-0.421	Destabilizing	1.0	D	0.785	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.