TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23811	71656;71657;71658	chr2:178574701;178574700;178574699	chr2:179439428;179439427;179439426
N2AB	22170	66733;66734;66735	chr2:178574701;178574700;178574699	chr2:179439428;179439427;179439426
N2A	21243	63952;63953;63954	chr2:178574701;178574700;178574699	chr2:179439428;179439427;179439426
N2B	14746	44461;44462;44463	chr2:178574701;178574700;178574699	chr2:179439428;179439427;179439426
Novex-1	14871	44836;44837;44838	chr2:178574701;178574700;178574699	chr2:179439428;179439427;179439426
Novex-2	14938	45037;45038;45039	chr2:178574701;178574700;178574699	chr2:179439428;179439427;179439426
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-60
• Domain position: 86
• Structural Position: 119
• Q(SASA): 0.3302
• 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
P/S	None	None	1.0	N	0.795	0.436	0.385578977469	gnomAD-4.0.0	1.36878E-06	None	None	None	None	N	None	2.98918E-05	0	None	0	0	None	0	0	0	1.16025E-05	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
P/A	0.1084	likely_benign	0.0952	benign	-1.152	Destabilizing	1.0	D	0.782	deleterious	N	0.483080936	None	None	N
P/C	0.5824	likely_pathogenic	0.4934	ambiguous	-0.779	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
P/D	0.4732	ambiguous	0.3882	ambiguous	-0.882	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
P/E	0.2859	likely_benign	0.2393	benign	-0.942	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
P/F	0.5657	likely_pathogenic	0.4758	ambiguous	-0.963	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
P/G	0.3827	ambiguous	0.3069	benign	-1.388	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
P/H	0.2558	likely_benign	0.2147	benign	-0.807	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
P/I	0.3648	ambiguous	0.3133	benign	-0.634	Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
P/K	0.3232	likely_benign	0.2633	benign	-0.996	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
P/L	0.1537	likely_benign	0.1366	benign	-0.634	Destabilizing	1.0	D	0.82	deleterious	N	0.49695431	None	None	N
P/M	0.3265	likely_benign	0.284	benign	-0.503	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
P/N	0.3513	ambiguous	0.2755	benign	-0.71	Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
P/Q	0.1867	likely_benign	0.1594	benign	-0.956	Destabilizing	1.0	D	0.831	deleterious	N	0.489449548	None	None	N
P/R	0.2571	likely_benign	0.2173	benign	-0.375	Destabilizing	1.0	D	0.852	deleterious	N	0.494740724	None	None	N
P/S	0.1713	likely_benign	0.1395	benign	-1.162	Destabilizing	1.0	D	0.795	deleterious	N	0.485659881	None	None	N
P/T	0.1305	likely_benign	0.1173	benign	-1.124	Destabilizing	1.0	D	0.797	deleterious	N	0.501552053	None	None	N
P/V	0.2439	likely_benign	0.2097	benign	-0.771	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
P/W	0.7414	likely_pathogenic	0.6555	pathogenic	-1.051	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
P/Y	0.5346	ambiguous	0.4444	ambiguous	-0.801	Destabilizing	1.0	D	0.846	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.