TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29111	87556;87557;87558	chr2:178558023;178558022;178558021	chr2:179422750;179422749;179422748
N2AB	27470	82633;82634;82635	chr2:178558023;178558022;178558021	chr2:179422750;179422749;179422748
N2A	26543	79852;79853;79854	chr2:178558023;178558022;178558021	chr2:179422750;179422749;179422748
N2B	20046	60361;60362;60363	chr2:178558023;178558022;178558021	chr2:179422750;179422749;179422748
Novex-1	20171	60736;60737;60738	chr2:178558023;178558022;178558021	chr2:179422750;179422749;179422748
Novex-2	20238	60937;60938;60939	chr2:178558023;178558022;178558021	chr2:179422750;179422749;179422748
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-145
• Domain position: 67
• Structural Position: 149
• Q(SASA): 0.1524
• 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
D/A	None	None	1.0	D	0.831	0.877	0.816108210376	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-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
D/A	0.9555	likely_pathogenic	0.9576	pathogenic	-0.005	Destabilizing	1.0	D	0.831	deleterious	D	0.600225535	None	None	N
D/C	0.9861	likely_pathogenic	0.9844	pathogenic	0.181	Stabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
D/E	0.9265	likely_pathogenic	0.9235	pathogenic	-0.635	Destabilizing	1.0	D	0.582	neutral	D	0.566743823	None	None	N
D/F	0.9914	likely_pathogenic	0.9913	pathogenic	0.616	Stabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
D/G	0.9639	likely_pathogenic	0.9672	pathogenic	-0.46	Destabilizing	1.0	D	0.772	deleterious	D	0.60042734	None	None	N
D/H	0.9563	likely_pathogenic	0.9397	pathogenic	0.296	Stabilizing	1.0	D	0.834	deleterious	D	0.559071671	None	None	N
D/I	0.9896	likely_pathogenic	0.9893	pathogenic	1.223	Stabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
D/K	0.9908	likely_pathogenic	0.9905	pathogenic	0.175	Stabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
D/L	0.9834	likely_pathogenic	0.9834	pathogenic	1.223	Stabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
D/M	0.9942	likely_pathogenic	0.994	pathogenic	1.671	Stabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
D/N	0.9004	likely_pathogenic	0.8843	pathogenic	-0.627	Destabilizing	1.0	D	0.768	deleterious	D	0.598611101	None	None	N
D/P	0.9971	likely_pathogenic	0.997	pathogenic	0.842	Stabilizing	1.0	D	0.814	deleterious	None	None	None	None	N
D/Q	0.9847	likely_pathogenic	0.9833	pathogenic	-0.336	Destabilizing	1.0	D	0.752	deleterious	None	None	None	None	N
D/R	0.99	likely_pathogenic	0.99	pathogenic	0.205	Stabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
D/S	0.9302	likely_pathogenic	0.9266	pathogenic	-0.926	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
D/T	0.98	likely_pathogenic	0.9778	pathogenic	-0.507	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
D/V	0.9651	likely_pathogenic	0.9667	pathogenic	0.842	Stabilizing	1.0	D	0.837	deleterious	D	0.600830948	None	None	N
D/W	0.9975	likely_pathogenic	0.9974	pathogenic	0.745	Stabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
D/Y	0.9408	likely_pathogenic	0.9401	pathogenic	0.918	Stabilizing	1.0	D	0.855	deleterious	D	0.600629144	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.