TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23883	71872;71873;71874	chr2:178574485;178574484;178574483	chr2:179439212;179439211;179439210
N2AB	22242	66949;66950;66951	chr2:178574485;178574484;178574483	chr2:179439212;179439211;179439210
N2A	21315	64168;64169;64170	chr2:178574485;178574484;178574483	chr2:179439212;179439211;179439210
N2B	14818	44677;44678;44679	chr2:178574485;178574484;178574483	chr2:179439212;179439211;179439210
Novex-1	14943	45052;45053;45054	chr2:178574485;178574484;178574483	chr2:179439212;179439211;179439210
Novex-2	15010	45253;45254;45255	chr2:178574485;178574484;178574483	chr2:179439212;179439211;179439210
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Fn3-61
• Domain position: 58
• Structural Position: 88
• Q(SASA): 0.2344
• 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/S	None	None	0.997	N	0.675	0.453	0.267755039894	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.9375E-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	0.2016	likely_benign	0.2227	benign	-0.43	Destabilizing	0.983	D	0.557	neutral	N	0.468399485	None	None	N
G/C	0.2954	likely_benign	0.3214	benign	-0.484	Destabilizing	0.652	D	0.656	neutral	N	0.47286695	None	None	N
G/D	0.2876	likely_benign	0.3291	benign	-0.947	Destabilizing	1.0	D	0.785	deleterious	N	0.385303673	None	None	N
G/E	0.2841	likely_benign	0.3349	benign	-0.935	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
G/F	0.7145	likely_pathogenic	0.74	pathogenic	-0.691	Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
G/H	0.4888	ambiguous	0.5361	ambiguous	-1.056	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
G/I	0.557	ambiguous	0.6143	pathogenic	0.07	Stabilizing	0.998	D	0.809	deleterious	None	None	None	None	N
G/K	0.4738	ambiguous	0.5284	ambiguous	-0.923	Destabilizing	0.999	D	0.803	deleterious	None	None	None	None	N
G/L	0.5437	ambiguous	0.6053	pathogenic	0.07	Stabilizing	0.996	D	0.807	deleterious	None	None	None	None	N
G/M	0.6079	likely_pathogenic	0.653	pathogenic	-0.066	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
G/N	0.319	likely_benign	0.3572	ambiguous	-0.733	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
G/P	0.9277	likely_pathogenic	0.9429	pathogenic	-0.056	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
G/Q	0.3592	ambiguous	0.4157	ambiguous	-0.795	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
G/R	0.3749	ambiguous	0.4182	ambiguous	-0.739	Destabilizing	1.0	D	0.791	deleterious	N	0.481827355	None	None	N
G/S	0.1332	likely_benign	0.1452	benign	-0.976	Destabilizing	0.997	D	0.675	neutral	N	0.460492078	None	None	N
G/T	0.2561	likely_benign	0.289	benign	-0.87	Destabilizing	0.998	D	0.79	deleterious	None	None	None	None	N
G/V	0.363	ambiguous	0.4237	ambiguous	-0.056	Destabilizing	0.997	D	0.81	deleterious	N	0.477848475	None	None	N
G/W	0.6046	likely_pathogenic	0.6249	pathogenic	-1.186	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
G/Y	0.5907	likely_pathogenic	0.6173	pathogenic	-0.652	Destabilizing	1.0	D	0.811	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.