TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19251	57976;57977;57978	chr2:178595603;178595602;178595601	chr2:179460330;179460329;179460328
N2AB	17610	53053;53054;53055	chr2:178595603;178595602;178595601	chr2:179460330;179460329;179460328
N2A	16683	50272;50273;50274	chr2:178595603;178595602;178595601	chr2:179460330;179460329;179460328
N2B	10186	30781;30782;30783	chr2:178595603;178595602;178595601	chr2:179460330;179460329;179460328
Novex-1	10311	31156;31157;31158	chr2:178595603;178595602;178595601	chr2:179460330;179460329;179460328
Novex-2	10378	31357;31358;31359	chr2:178595603;178595602;178595601	chr2:179460330;179460329;179460328
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Fn3-27
• Domain position: 69
• Structural Position: 100
• Q(SASA): 0.3061
• 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	rs2051353866	None	1.0	N	0.839	0.576	0.610686279038	gnomAD-4.0.0	1.65076E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.09674E-05

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	0.6129	likely_pathogenic	0.6487	pathogenic	-0.397	Destabilizing	1.0	D	0.715	prob.delet.	D	0.526818644	None	None	N
G/C	0.7079	likely_pathogenic	0.7407	pathogenic	-0.888	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
G/D	0.2647	likely_benign	0.3776	ambiguous	-0.824	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
G/E	0.4302	ambiguous	0.503	ambiguous	-0.93	Destabilizing	1.0	D	0.839	deleterious	N	0.488065278	None	None	N
G/F	0.9496	likely_pathogenic	0.9629	pathogenic	-0.832	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	N
G/H	0.7372	likely_pathogenic	0.7995	pathogenic	-0.739	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
G/I	0.9609	likely_pathogenic	0.9678	pathogenic	-0.28	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
G/K	0.8201	likely_pathogenic	0.8533	pathogenic	-1.162	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
G/L	0.9148	likely_pathogenic	0.9298	pathogenic	-0.28	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
G/M	0.9155	likely_pathogenic	0.9321	pathogenic	-0.414	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
G/N	0.3236	likely_benign	0.3811	ambiguous	-0.83	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	N
G/P	0.9917	likely_pathogenic	0.9915	pathogenic	-0.281	Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	N
G/Q	0.6306	likely_pathogenic	0.6846	pathogenic	-1.048	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
G/R	0.7717	likely_pathogenic	0.8222	pathogenic	-0.718	Destabilizing	1.0	D	0.831	deleterious	N	0.501498725	None	None	N
G/S	0.2736	likely_benign	0.3288	benign	-1.005	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	N
G/T	0.6885	likely_pathogenic	0.7333	pathogenic	-1.036	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
G/V	0.9108	likely_pathogenic	0.928	pathogenic	-0.281	Destabilizing	1.0	D	0.813	deleterious	N	0.509007143	None	None	N
G/W	0.8459	likely_pathogenic	0.9024	pathogenic	-1.103	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
G/Y	0.8453	likely_pathogenic	0.8924	pathogenic	-0.724	Destabilizing	1.0	D	0.788	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.