TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22289	67090;67091;67092	chr2:178580514;178580513;178580512	chr2:179445241;179445240;179445239
N2AB	20648	62167;62168;62169	chr2:178580514;178580513;178580512	chr2:179445241;179445240;179445239
N2A	19721	59386;59387;59388	chr2:178580514;178580513;178580512	chr2:179445241;179445240;179445239
N2B	13224	39895;39896;39897	chr2:178580514;178580513;178580512	chr2:179445241;179445240;179445239
Novex-1	13349	40270;40271;40272	chr2:178580514;178580513;178580512	chr2:179445241;179445240;179445239
Novex-2	13416	40471;40472;40473	chr2:178580514;178580513;178580512	chr2:179445241;179445240;179445239
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-126
• Domain position: 25
• Structural Position: 42
• Q(SASA): 0.4684
• 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
P/L	rs751203353	-0.187	1.0	D	0.722	0.72	0.773713791686	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
P/L	rs751203353	-0.187	1.0	D	0.722	0.72	0.773713791686	gnomAD-4.0.0	1.59339E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43357E-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
P/A	0.9511	likely_pathogenic	0.9501	pathogenic	-0.515	Destabilizing	1.0	D	0.686	prob.neutral	D	0.565076741	None	None	I
P/C	0.9939	likely_pathogenic	0.9943	pathogenic	-0.442	Destabilizing	1.0	D	0.758	deleterious	None	None	None	None	I
P/D	0.9888	likely_pathogenic	0.9868	pathogenic	-0.457	Destabilizing	1.0	D	0.686	prob.neutral	None	None	None	None	I
P/E	0.9879	likely_pathogenic	0.9863	pathogenic	-0.585	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	I
P/F	0.9963	likely_pathogenic	0.9959	pathogenic	-0.837	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	I
P/G	0.987	likely_pathogenic	0.9857	pathogenic	-0.642	Destabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	I
P/H	0.9807	likely_pathogenic	0.98	pathogenic	-0.311	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	I
P/I	0.9684	likely_pathogenic	0.9692	pathogenic	-0.332	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	I
P/K	0.9839	likely_pathogenic	0.9827	pathogenic	-0.446	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	I
P/L	0.9235	likely_pathogenic	0.9225	pathogenic	-0.332	Destabilizing	1.0	D	0.722	prob.delet.	D	0.625940475	None	None	I
P/M	0.9787	likely_pathogenic	0.9802	pathogenic	-0.261	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	I
P/N	0.9842	likely_pathogenic	0.9822	pathogenic	-0.071	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	I
P/Q	0.9799	likely_pathogenic	0.9788	pathogenic	-0.357	Destabilizing	1.0	D	0.696	prob.neutral	D	0.565076741	None	None	I
P/R	0.9758	likely_pathogenic	0.9753	pathogenic	0.097	Stabilizing	1.0	D	0.743	deleterious	D	0.625536867	None	None	I
P/S	0.9794	likely_pathogenic	0.9786	pathogenic	-0.389	Destabilizing	1.0	D	0.693	prob.neutral	D	0.564569762	None	None	I
P/T	0.9516	likely_pathogenic	0.9528	pathogenic	-0.423	Destabilizing	1.0	D	0.689	prob.neutral	D	0.625536867	None	None	I
P/V	0.9554	likely_pathogenic	0.9556	pathogenic	-0.358	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	I
P/W	0.999	likely_pathogenic	0.999	pathogenic	-0.921	Destabilizing	1.0	D	0.758	deleterious	None	None	None	None	I
P/Y	0.9949	likely_pathogenic	0.9948	pathogenic	-0.618	Destabilizing	1.0	D	0.767	deleterious	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.