TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27154	81685;81686;81687	chr2:178564672;178564671;178564670	chr2:179429399;179429398;179429397
N2AB	25513	76762;76763;76764	chr2:178564672;178564671;178564670	chr2:179429399;179429398;179429397
N2A	24586	73981;73982;73983	chr2:178564672;178564671;178564670	chr2:179429399;179429398;179429397
N2B	18089	54490;54491;54492	chr2:178564672;178564671;178564670	chr2:179429399;179429398;179429397
Novex-1	18214	54865;54866;54867	chr2:178564672;178564671;178564670	chr2:179429399;179429398;179429397
Novex-2	18281	55066;55067;55068	chr2:178564672;178564671;178564670	chr2:179429399;179429398;179429397
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Fn3-85
• Domain position: 83
• Structural Position: 115
• Q(SASA): 0.1385
• 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
G/S	None	None	1.0	D	0.833	0.719	0.542452414656	gnomAD-4.0.0	1.592E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43303E-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
G/A	0.8553	likely_pathogenic	0.862	pathogenic	-0.737	Destabilizing	1.0	D	0.741	deleterious	D	0.556783584	None	None	I
G/C	0.9245	likely_pathogenic	0.9317	pathogenic	-1.004	Destabilizing	1.0	D	0.851	deleterious	D	0.569407337	None	None	I
G/D	0.9724	likely_pathogenic	0.9729	pathogenic	-1.27	Destabilizing	1.0	D	0.897	deleterious	D	0.544755716	None	None	I
G/E	0.9856	likely_pathogenic	0.9862	pathogenic	-1.382	Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	I
G/F	0.9926	likely_pathogenic	0.9937	pathogenic	-1.166	Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	I
G/H	0.9854	likely_pathogenic	0.987	pathogenic	-1.109	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	I
G/I	0.9924	likely_pathogenic	0.9931	pathogenic	-0.59	Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	I
G/K	0.9837	likely_pathogenic	0.9851	pathogenic	-1.365	Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	I
G/L	0.989	likely_pathogenic	0.9896	pathogenic	-0.59	Destabilizing	1.0	D	0.868	deleterious	None	None	None	None	I
G/M	0.9931	likely_pathogenic	0.9934	pathogenic	-0.501	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	I
G/N	0.9673	likely_pathogenic	0.9686	pathogenic	-0.997	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	I
G/P	0.9986	likely_pathogenic	0.9984	pathogenic	-0.601	Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	I
G/Q	0.9793	likely_pathogenic	0.981	pathogenic	-1.279	Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	I
G/R	0.9577	likely_pathogenic	0.96	pathogenic	-0.859	Destabilizing	1.0	D	0.9	deleterious	D	0.557037074	None	None	I
G/S	0.7515	likely_pathogenic	0.7688	pathogenic	-1.168	Destabilizing	1.0	D	0.833	deleterious	D	0.567632911	None	None	I
G/T	0.9506	likely_pathogenic	0.9511	pathogenic	-1.219	Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	I
G/V	0.9831	likely_pathogenic	0.9845	pathogenic	-0.601	Destabilizing	1.0	D	0.881	deleterious	D	0.545769674	None	None	I
G/W	0.9852	likely_pathogenic	0.9855	pathogenic	-1.397	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	I
G/Y	0.9869	likely_pathogenic	0.9889	pathogenic	-1.059	Destabilizing	1.0	D	0.883	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.