TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18660	56203;56204;56205	chr2:178600926;178600925;178600924	chr2:179465653;179465652;179465651
N2AB	17019	51280;51281;51282	chr2:178600926;178600925;178600924	chr2:179465653;179465652;179465651
N2A	16092	48499;48500;48501	chr2:178600926;178600925;178600924	chr2:179465653;179465652;179465651
N2B	9595	29008;29009;29010	chr2:178600926;178600925;178600924	chr2:179465653;179465652;179465651
Novex-1	9720	29383;29384;29385	chr2:178600926;178600925;178600924	chr2:179465653;179465652;179465651
Novex-2	9787	29584;29585;29586	chr2:178600926;178600925;178600924	chr2:179465653;179465652;179465651
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-23
• Domain position: 82
• Structural Position: 109
• Q(SASA): 0.1428
• 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
K/N	rs776347511	None	0.982	N	0.62	0.333	0.18274738541	gnomAD-4.0.0	6.84524E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99818E-07	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
K/A	0.7154	likely_pathogenic	0.7494	pathogenic	-1.238	Destabilizing	0.953	D	0.667	neutral	None	None	None	None	N
K/C	0.7244	likely_pathogenic	0.7315	pathogenic	-1.604	Destabilizing	0.999	D	0.787	deleterious	None	None	None	None	N
K/D	0.9705	likely_pathogenic	0.9785	pathogenic	-1.91	Destabilizing	0.993	D	0.659	neutral	None	None	None	None	N
K/E	0.6441	likely_pathogenic	0.7085	pathogenic	-1.683	Destabilizing	0.939	D	0.669	neutral	N	0.476141725	None	None	N
K/F	0.9088	likely_pathogenic	0.9134	pathogenic	-0.554	Destabilizing	0.993	D	0.814	deleterious	None	None	None	None	N
K/G	0.8763	likely_pathogenic	0.9051	pathogenic	-1.651	Destabilizing	0.993	D	0.699	prob.neutral	None	None	None	None	N
K/H	0.6021	likely_pathogenic	0.6265	pathogenic	-1.977	Destabilizing	0.998	D	0.681	prob.neutral	None	None	None	None	N
K/I	0.6429	likely_pathogenic	0.6572	pathogenic	-0.102	Destabilizing	0.964	D	0.743	deleterious	N	0.449179006	None	None	N
K/L	0.6075	likely_pathogenic	0.6094	pathogenic	-0.102	Destabilizing	0.91	D	0.697	prob.neutral	None	None	None	None	N
K/M	0.334	likely_benign	0.3601	ambiguous	-0.519	Destabilizing	0.998	D	0.685	prob.neutral	None	None	None	None	N
K/N	0.8876	likely_pathogenic	0.9134	pathogenic	-1.828	Destabilizing	0.982	D	0.62	neutral	N	0.477409172	None	None	N
K/P	0.9962	likely_pathogenic	0.9973	pathogenic	-0.458	Destabilizing	0.998	D	0.683	prob.neutral	None	None	None	None	N
K/Q	0.2859	likely_benign	0.3151	benign	-1.572	Destabilizing	0.982	D	0.628	neutral	N	0.504048067	None	None	N
K/R	0.0943	likely_benign	0.0962	benign	-1.519	Destabilizing	0.1	N	0.501	neutral	N	0.424357919	None	None	N
K/S	0.7615	likely_pathogenic	0.8033	pathogenic	-2.235	Highly Destabilizing	0.953	D	0.659	neutral	None	None	None	None	N
K/T	0.4688	ambiguous	0.5232	ambiguous	-1.797	Destabilizing	0.939	D	0.643	neutral	N	0.477845688	None	None	N
K/V	0.5935	likely_pathogenic	0.5966	pathogenic	-0.458	Destabilizing	0.386	N	0.588	neutral	None	None	None	None	N
K/W	0.8972	likely_pathogenic	0.9104	pathogenic	-0.725	Destabilizing	0.999	D	0.739	prob.delet.	None	None	None	None	N
K/Y	0.8204	likely_pathogenic	0.8505	pathogenic	-0.346	Destabilizing	0.998	D	0.77	deleterious	None	None	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.