TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9736	29431;29432;29433	chr2:178706668;178706667;178706666	chr2:179571395;179571394;179571393
N2AB	9419	28480;28481;28482	chr2:178706668;178706667;178706666	chr2:179571395;179571394;179571393
N2A	8492	25699;25700;25701	chr2:178706668;178706667;178706666	chr2:179571395;179571394;179571393
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: W
• RefSeq wild type transcript codon: TGG
• RefSeq wild type template codon: ACC
• Domain: Ig-83
• Domain position: 39
• Structural Position: 53
• Q(SASA): 1.1957
• Predicted PPI site: I

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
W/G	rs1229199576	-0.29	1.0	None	0.606	0.48	0.36076525451	gnomAD-2.1.1	4.01E-06	None	None	None	None	I	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
W/G	rs1229199576	-0.29	1.0	None	0.606	0.48	0.36076525451	gnomAD-4.0.0	1.59121E-06	None	None	None	None	I	None	0	2.28645E-05	None	0	0	None	0	0	0	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
W/A	0.9884	likely_pathogenic	0.9717	pathogenic	-0.376	Destabilizing	1.0	D	0.667	neutral	None	None	None	None	I
W/C	0.9972	likely_pathogenic	0.9929	pathogenic	0.243	Stabilizing	1.0	D	0.676	prob.neutral	None	None	None	None	I
W/D	0.9964	likely_pathogenic	0.9925	pathogenic	0.884	Stabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	I
W/E	0.9976	likely_pathogenic	0.9941	pathogenic	0.896	Stabilizing	1.0	D	0.684	prob.neutral	None	None	None	None	I
W/F	0.7235	likely_pathogenic	0.6253	pathogenic	-0.181	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	I
W/G	0.9412	likely_pathogenic	0.8782	pathogenic	-0.49	Destabilizing	1.0	D	0.606	neutral	None	None	None	None	I
W/H	0.9913	likely_pathogenic	0.9827	pathogenic	0.316	Stabilizing	1.0	D	0.656	neutral	None	None	None	None	I
W/I	0.9808	likely_pathogenic	0.959	pathogenic	-0.072	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	I
W/K	0.9985	likely_pathogenic	0.9956	pathogenic	0.381	Stabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	I
W/L	0.9564	likely_pathogenic	0.9081	pathogenic	-0.072	Destabilizing	1.0	D	0.606	neutral	None	None	None	None	I
W/M	0.9851	likely_pathogenic	0.9651	pathogenic	-0.088	Destabilizing	1.0	D	0.658	neutral	None	None	None	None	I
W/N	0.9941	likely_pathogenic	0.9866	pathogenic	0.101	Stabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	I
W/P	0.9972	likely_pathogenic	0.9926	pathogenic	-0.165	Destabilizing	1.0	D	0.694	prob.neutral	None	None	None	None	I
W/Q	0.9984	likely_pathogenic	0.9954	pathogenic	0.25	Stabilizing	1.0	D	0.649	neutral	None	None	None	None	I
W/R	0.9977	likely_pathogenic	0.9932	pathogenic	0.337	Stabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	I
W/S	0.9806	likely_pathogenic	0.9494	pathogenic	-0.229	Destabilizing	1.0	D	0.676	prob.neutral	None	None	None	None	I
W/T	0.9899	likely_pathogenic	0.9757	pathogenic	-0.167	Destabilizing	1.0	D	0.625	neutral	None	None	None	None	I
W/V	0.9818	likely_pathogenic	0.9588	pathogenic	-0.165	Destabilizing	1.0	D	0.671	neutral	None	None	None	None	I
W/Y	0.8903	likely_pathogenic	0.8234	pathogenic	-0.368	Destabilizing	1.0	D	0.658	neutral	None	None	None	None	I

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.