TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21801	65626;65627;65628	chr2:178583781;178583780;178583779	chr2:179448508;179448507;179448506
N2AB	20160	60703;60704;60705	chr2:178583781;178583780;178583779	chr2:179448508;179448507;179448506
N2A	19233	57922;57923;57924	chr2:178583781;178583780;178583779	chr2:179448508;179448507;179448506
N2B	12736	38431;38432;38433	chr2:178583781;178583780;178583779	chr2:179448508;179448507;179448506
Novex-1	12861	38806;38807;38808	chr2:178583781;178583780;178583779	chr2:179448508;179448507;179448506
Novex-2	12928	39007;39008;39009	chr2:178583781;178583780;178583779	chr2:179448508;179448507;179448506
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGT
• RefSeq wild type template codon: CCA
• Domain: Fn3-46
• Domain position: 45
• Structural Position: 60
• Q(SASA): 0.4087
• 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/D	None	None	0.811	N	0.306	0.27	0.239305524855	gnomAD-4.0.0	1.59823E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86832E-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	0.1685	likely_benign	0.146	benign	-0.279	Destabilizing	0.64	D	0.361	neutral	N	0.459569358	None	None	N
G/C	0.3363	likely_benign	0.2808	benign	-0.871	Destabilizing	0.125	N	0.434	neutral	N	0.499364995	None	None	N
G/D	0.2032	likely_benign	0.1868	benign	-0.751	Destabilizing	0.811	D	0.306	neutral	N	0.459163926	None	None	N
G/E	0.204	likely_benign	0.181	benign	-0.919	Destabilizing	0.132	N	0.261	neutral	None	None	None	None	N
G/F	0.6587	likely_pathogenic	0.6279	pathogenic	-1.058	Destabilizing	0.988	D	0.553	neutral	None	None	None	None	N
G/H	0.4552	ambiguous	0.4282	ambiguous	-0.489	Destabilizing	0.999	D	0.496	neutral	None	None	None	None	N
G/I	0.459	ambiguous	0.3886	ambiguous	-0.486	Destabilizing	0.976	D	0.55	neutral	None	None	None	None	N
G/K	0.3938	ambiguous	0.3825	ambiguous	-0.86	Destabilizing	0.919	D	0.391	neutral	None	None	None	None	N
G/L	0.496	ambiguous	0.4321	ambiguous	-0.486	Destabilizing	0.952	D	0.511	neutral	None	None	None	None	N
G/M	0.517	ambiguous	0.4797	ambiguous	-0.569	Destabilizing	0.999	D	0.57	neutral	None	None	None	None	N
G/N	0.2644	likely_benign	0.2528	benign	-0.469	Destabilizing	0.976	D	0.368	neutral	None	None	None	None	N
G/P	0.7955	likely_pathogenic	0.7788	pathogenic	-0.387	Destabilizing	0.988	D	0.481	neutral	None	None	None	None	N
G/Q	0.3211	likely_benign	0.2965	benign	-0.766	Destabilizing	0.976	D	0.47	neutral	None	None	None	None	N
G/R	0.3231	likely_benign	0.3036	benign	-0.388	Destabilizing	0.968	D	0.471	neutral	N	0.515769357	None	None	N
G/S	0.1287	likely_benign	0.1078	benign	-0.568	Destabilizing	0.251	N	0.239	neutral	N	0.424165918	None	None	N
G/T	0.1802	likely_benign	0.1565	benign	-0.675	Destabilizing	0.851	D	0.392	neutral	None	None	None	None	N
G/V	0.2963	likely_benign	0.2379	benign	-0.387	Destabilizing	0.968	D	0.513	neutral	N	0.519695097	None	None	N
G/W	0.5305	ambiguous	0.4886	ambiguous	-1.195	Destabilizing	0.999	D	0.595	neutral	None	None	None	None	N
G/Y	0.5562	ambiguous	0.5051	ambiguous	-0.87	Destabilizing	0.996	D	0.555	neutral	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.