TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26413	79462;79463;79464	chr2:178566895;178566894;178566893	chr2:179431622;179431621;179431620
N2AB	24772	74539;74540;74541	chr2:178566895;178566894;178566893	chr2:179431622;179431621;179431620
N2A	23845	71758;71759;71760	chr2:178566895;178566894;178566893	chr2:179431622;179431621;179431620
N2B	17348	52267;52268;52269	chr2:178566895;178566894;178566893	chr2:179431622;179431621;179431620
Novex-1	17473	52642;52643;52644	chr2:178566895;178566894;178566893	chr2:179431622;179431621;179431620
Novex-2	17540	52843;52844;52845	chr2:178566895;178566894;178566893	chr2:179431622;179431621;179431620
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: 28
• Structural Position: 30
• Q(SASA): 0.3724
• 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
D/E	None	None	0.989	N	0.499	0.299	0.469165163779	gnomAD-4.0.0	6.8429E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	1.7337E-04	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
D/A	0.8307	likely_pathogenic	0.8003	pathogenic	-0.357	Destabilizing	0.989	D	0.639	neutral	N	0.496843327	None	None	I
D/C	0.9668	likely_pathogenic	0.9685	pathogenic	0.228	Stabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	I
D/E	0.8455	likely_pathogenic	0.8273	pathogenic	-0.494	Destabilizing	0.989	D	0.499	neutral	N	0.50504608	None	None	I
D/F	0.9819	likely_pathogenic	0.9793	pathogenic	-0.555	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	I
D/G	0.8261	likely_pathogenic	0.7974	pathogenic	-0.576	Destabilizing	0.989	D	0.574	neutral	N	0.510872658	None	None	I
D/H	0.9054	likely_pathogenic	0.9118	pathogenic	-0.793	Destabilizing	1.0	D	0.643	neutral	N	0.51291012	None	None	I
D/I	0.9539	likely_pathogenic	0.9571	pathogenic	0.18	Stabilizing	0.998	D	0.739	prob.delet.	None	None	None	None	I
D/K	0.9728	likely_pathogenic	0.9648	pathogenic	0.325	Stabilizing	0.998	D	0.566	neutral	None	None	None	None	I
D/L	0.945	likely_pathogenic	0.944	pathogenic	0.18	Stabilizing	0.998	D	0.667	neutral	None	None	None	None	I
D/M	0.977	likely_pathogenic	0.9761	pathogenic	0.613	Stabilizing	1.0	D	0.714	prob.delet.	None	None	None	None	I
D/N	0.1596	likely_benign	0.2185	benign	0.043	Stabilizing	0.733	D	0.237	neutral	D	0.523042046	None	None	I
D/P	0.9771	likely_pathogenic	0.9684	pathogenic	0.024	Stabilizing	1.0	D	0.643	neutral	None	None	None	None	I
D/Q	0.9544	likely_pathogenic	0.947	pathogenic	0.073	Stabilizing	0.999	D	0.588	neutral	None	None	None	None	I
D/R	0.9701	likely_pathogenic	0.9627	pathogenic	0.226	Stabilizing	0.999	D	0.718	prob.delet.	None	None	None	None	I
D/S	0.4426	ambiguous	0.4419	ambiguous	-0.069	Destabilizing	0.983	D	0.567	neutral	None	None	None	None	I
D/T	0.6518	likely_pathogenic	0.6351	pathogenic	0.111	Stabilizing	0.611	D	0.297	neutral	None	None	None	None	I
D/V	0.8859	likely_pathogenic	0.8806	pathogenic	0.024	Stabilizing	0.997	D	0.668	neutral	D	0.522442773	None	None	I
D/W	0.9968	likely_pathogenic	0.9963	pathogenic	-0.492	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	I
D/Y	0.9013	likely_pathogenic	0.8913	pathogenic	-0.322	Destabilizing	0.999	D	0.733	prob.delet.	D	0.541814476	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.