TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26454	79585;79586;79587	chr2:178566772;178566771;178566770	chr2:179431499;179431498;179431497
N2AB	24813	74662;74663;74664	chr2:178566772;178566771;178566770	chr2:179431499;179431498;179431497
N2A	23886	71881;71882;71883	chr2:178566772;178566771;178566770	chr2:179431499;179431498;179431497
N2B	17389	52390;52391;52392	chr2:178566772;178566771;178566770	chr2:179431499;179431498;179431497
Novex-1	17514	52765;52766;52767	chr2:178566772;178566771;178566770	chr2:179431499;179431498;179431497
Novex-2	17581	52966;52967;52968	chr2:178566772;178566771;178566770	chr2:179431499;179431498;179431497
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-80
• Domain position: 69
• Structural Position: 100
• Q(SASA): 0.4838
• 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/Y	None	None	1.0	N	0.884	0.507	0.594593949059	gnomAD-4.0.0	1.59213E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43283E-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	0.176	likely_benign	0.1985	benign	-0.378	Destabilizing	1.0	D	0.861	deleterious	N	0.494988654	None	None	N
D/C	0.5734	likely_pathogenic	0.606	pathogenic	-0.109	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
D/E	0.15	likely_benign	0.148	benign	-0.412	Destabilizing	1.0	D	0.524	neutral	N	0.517884156	None	None	N
D/F	0.5289	ambiguous	0.5436	ambiguous	-0.448	Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	N
D/G	0.0972	likely_benign	0.0999	benign	-0.604	Destabilizing	1.0	D	0.791	deleterious	N	0.357953995	None	None	N
D/H	0.2979	likely_benign	0.3422	ambiguous	-0.609	Destabilizing	1.0	D	0.84	deleterious	N	0.50316542	None	None	N
D/I	0.4752	ambiguous	0.5199	ambiguous	0.18	Stabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
D/K	0.4261	ambiguous	0.4827	ambiguous	-0.43	Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
D/L	0.3764	ambiguous	0.4218	ambiguous	0.18	Stabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
D/M	0.5612	ambiguous	0.5863	pathogenic	0.447	Stabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
D/N	0.0892	likely_benign	0.0893	benign	-0.382	Destabilizing	1.0	D	0.803	deleterious	N	0.421202971	None	None	N
D/P	0.8557	likely_pathogenic	0.8899	pathogenic	0.016	Stabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
D/Q	0.3389	likely_benign	0.3734	ambiguous	-0.337	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
D/R	0.4712	ambiguous	0.5266	ambiguous	-0.261	Destabilizing	1.0	D	0.919	deleterious	None	None	None	None	N
D/S	0.1313	likely_benign	0.1373	benign	-0.603	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
D/T	0.2655	likely_benign	0.2888	benign	-0.453	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
D/V	0.3046	likely_benign	0.3389	benign	0.016	Stabilizing	1.0	D	0.902	deleterious	N	0.483752275	None	None	N
D/W	0.8445	likely_pathogenic	0.8623	pathogenic	-0.427	Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	N
D/Y	0.2141	likely_benign	0.2363	benign	-0.29	Destabilizing	1.0	D	0.884	deleterious	N	0.508629954	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.