TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17386	52381;52382;52383	chr2:178608855;178608854;178608853	chr2:179473582;179473581;179473580
N2AB	15745	47458;47459;47460	chr2:178608855;178608854;178608853	chr2:179473582;179473581;179473580
N2A	14818	44677;44678;44679	chr2:178608855;178608854;178608853	chr2:179473582;179473581;179473580
N2B	8321	25186;25187;25188	chr2:178608855;178608854;178608853	chr2:179473582;179473581;179473580
Novex-1	8446	25561;25562;25563	chr2:178608855;178608854;178608853	chr2:179473582;179473581;179473580
Novex-2	8513	25762;25763;25764	chr2:178608855;178608854;178608853	chr2:179473582;179473581;179473580
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Fn3-14
• Domain position: 18
• Structural Position: 20
• Q(SASA): 0.0758
• 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	rs1250473011	None	0.37	N	0.207	0.093	0.347217280506	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
V/I	rs1250473011	None	0.37	N	0.207	0.093	0.347217280506	gnomAD-4.0.0	6.57921E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.4718E-05	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	0.4729	ambiguous	0.4085	ambiguous	-1.964	Destabilizing	0.978	D	0.579	neutral	N	0.471229146	None	None	N
V/C	0.8	likely_pathogenic	0.7953	pathogenic	-1.789	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
V/D	0.9958	likely_pathogenic	0.9925	pathogenic	-2.441	Highly Destabilizing	0.999	D	0.865	deleterious	N	0.52099165	None	None	N
V/E	0.9903	likely_pathogenic	0.9846	pathogenic	-2.14	Highly Destabilizing	0.999	D	0.857	deleterious	None	None	None	None	N
V/F	0.6666	likely_pathogenic	0.5967	pathogenic	-1.166	Destabilizing	0.997	D	0.84	deleterious	N	0.478742753	None	None	N
V/G	0.7941	likely_pathogenic	0.735	pathogenic	-2.587	Highly Destabilizing	0.999	D	0.859	deleterious	N	0.520738161	None	None	N
V/H	0.9945	likely_pathogenic	0.9909	pathogenic	-2.547	Highly Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
V/I	0.1008	likely_benign	0.0949	benign	-0.185	Destabilizing	0.37	N	0.207	neutral	N	0.448405428	None	None	N
V/K	0.9926	likely_pathogenic	0.9879	pathogenic	-1.453	Destabilizing	0.999	D	0.857	deleterious	None	None	None	None	N
V/L	0.3854	ambiguous	0.346	ambiguous	-0.185	Destabilizing	0.9	D	0.473	neutral	N	0.491620274	None	None	N
V/M	0.3832	ambiguous	0.3155	benign	-0.552	Destabilizing	0.998	D	0.741	deleterious	None	None	None	None	N
V/N	0.9822	likely_pathogenic	0.9705	pathogenic	-2.007	Highly Destabilizing	0.999	D	0.887	deleterious	None	None	None	None	N
V/P	0.9934	likely_pathogenic	0.9896	pathogenic	-0.754	Destabilizing	0.999	D	0.868	deleterious	None	None	None	None	N
V/Q	0.9814	likely_pathogenic	0.9709	pathogenic	-1.66	Destabilizing	0.999	D	0.875	deleterious	None	None	None	None	N
V/R	0.9834	likely_pathogenic	0.9742	pathogenic	-1.649	Destabilizing	0.999	D	0.887	deleterious	None	None	None	None	N
V/S	0.8617	likely_pathogenic	0.8027	pathogenic	-2.682	Highly Destabilizing	0.999	D	0.847	deleterious	None	None	None	None	N
V/T	0.7326	likely_pathogenic	0.6599	pathogenic	-2.199	Highly Destabilizing	0.992	D	0.663	neutral	None	None	None	None	N
V/W	0.9955	likely_pathogenic	0.993	pathogenic	-1.67	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
V/Y	0.9703	likely_pathogenic	0.9591	pathogenic	-1.273	Destabilizing	0.999	D	0.842	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.