TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29635	89128;89129;89130	chr2:178554208;178554207;178554206	chr2:179418935;179418934;179418933
N2AB	27994	84205;84206;84207	chr2:178554208;178554207;178554206	chr2:179418935;179418934;179418933
N2A	27067	81424;81425;81426	chr2:178554208;178554207;178554206	chr2:179418935;179418934;179418933
N2B	20570	61933;61934;61935	chr2:178554208;178554207;178554206	chr2:179418935;179418934;179418933
Novex-1	20695	62308;62309;62310	chr2:178554208;178554207;178554206	chr2:179418935;179418934;179418933
Novex-2	20762	62509;62510;62511	chr2:178554208;178554207;178554206	chr2:179418935;179418934;179418933
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGG
• RefSeq wild type template codon: CCC
• Domain: Fn3-104
• Domain position: 3
• Structural Position: 3
• Q(SASA): 0.2071
• 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
G/E	rs1700410853	None	0.998	N	0.738	0.471	0.518199804421	gnomAD-4.0.0	2.40068E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.62504E-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
G/A	0.1919	likely_benign	0.2537	benign	-0.857	Destabilizing	0.962	D	0.652	neutral	N	0.479393727	None	None	N
G/C	0.327	likely_benign	0.4228	ambiguous	-1.172	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
G/D	0.4601	ambiguous	0.5386	ambiguous	-1.855	Destabilizing	0.998	D	0.742	deleterious	None	None	None	None	N
G/E	0.4692	ambiguous	0.5576	ambiguous	-1.9	Destabilizing	0.998	D	0.738	prob.delet.	N	0.492458326	None	None	N
G/F	0.7685	likely_pathogenic	0.8337	pathogenic	-1.165	Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	N
G/H	0.7269	likely_pathogenic	0.8121	pathogenic	-1.427	Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
G/I	0.5893	likely_pathogenic	0.6865	pathogenic	-0.464	Destabilizing	0.999	D	0.829	deleterious	None	None	None	None	N
G/K	0.7978	likely_pathogenic	0.8485	pathogenic	-1.351	Destabilizing	0.998	D	0.747	deleterious	None	None	None	None	N
G/L	0.5209	ambiguous	0.61	pathogenic	-0.464	Destabilizing	0.999	D	0.794	deleterious	None	None	None	None	N
G/M	0.6447	likely_pathogenic	0.7436	pathogenic	-0.462	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
G/N	0.5165	ambiguous	0.6	pathogenic	-1.129	Destabilizing	0.998	D	0.815	deleterious	None	None	None	None	N
G/P	0.9593	likely_pathogenic	0.9661	pathogenic	-0.556	Destabilizing	0.999	D	0.809	deleterious	None	None	None	None	N
G/Q	0.622	likely_pathogenic	0.7124	pathogenic	-1.347	Destabilizing	0.999	D	0.822	deleterious	None	None	None	None	N
G/R	0.7317	likely_pathogenic	0.7992	pathogenic	-1.034	Destabilizing	0.999	D	0.819	deleterious	N	0.505753642	None	None	N
G/S	0.1244	likely_benign	0.1553	benign	-1.324	Destabilizing	0.862	D	0.417	neutral	None	None	None	None	N
G/T	0.2945	likely_benign	0.3853	ambiguous	-1.305	Destabilizing	0.996	D	0.721	prob.delet.	None	None	None	None	N
G/V	0.458	ambiguous	0.5694	pathogenic	-0.556	Destabilizing	0.999	D	0.8	deleterious	N	0.512843987	None	None	N
G/W	0.7659	likely_pathogenic	0.8368	pathogenic	-1.521	Destabilizing	1.0	D	0.777	deleterious	D	0.524707271	None	None	N
G/Y	0.6735	likely_pathogenic	0.7628	pathogenic	-1.121	Destabilizing	1.0	D	0.841	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.