TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34066	102421;102422;102423	chr2:178534419;178534418;178534417	chr2:179399146;179399145;179399144
N2AB	32425	97498;97499;97500	chr2:178534419;178534418;178534417	chr2:179399146;179399145;179399144
N2A	31498	94717;94718;94719	chr2:178534419;178534418;178534417	chr2:179399146;179399145;179399144
N2B	25001	75226;75227;75228	chr2:178534419;178534418;178534417	chr2:179399146;179399145;179399144
Novex-1	25126	75601;75602;75603	chr2:178534419;178534418;178534417	chr2:179399146;179399145;179399144
Novex-2	25193	75802;75803;75804	chr2:178534419;178534418;178534417	chr2:179399146;179399145;179399144
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Kinase-1
• Domain position: 254
• Q(SASA): 0.2253
• 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
E/A	None	None	None	N	None	0.351	0.356281029322	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05

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
E/A	0.5207	ambiguous	0.4321	ambiguous	-0.505	Destabilizing	None	None	None	None	N	0.516089071	None	None	N
E/C	0.9891	likely_pathogenic	0.9827	pathogenic	0.073	Stabilizing	None	None	None	None	None	None	None	None	N
E/D	0.5318	ambiguous	0.4684	ambiguous	-0.511	Destabilizing	None	None	None	None	N	0.46200387	None	None	N
E/F	0.9786	likely_pathogenic	0.9585	pathogenic	-0.511	Destabilizing	None	None	None	None	None	None	None	None	N
E/G	0.6824	likely_pathogenic	0.6013	pathogenic	-0.736	Destabilizing	None	None	None	None	N	0.468145418	None	None	N
E/H	0.9303	likely_pathogenic	0.8823	pathogenic	-0.566	Destabilizing	None	None	None	None	None	None	None	None	N
E/I	0.9011	likely_pathogenic	0.8437	pathogenic	0.079	Stabilizing	None	None	None	None	None	None	None	None	N
E/K	0.607	likely_pathogenic	0.4557	ambiguous	0.1	Stabilizing	None	None	None	None	N	0.459738401	None	None	N
E/L	0.9001	likely_pathogenic	0.8467	pathogenic	0.079	Stabilizing	None	None	None	None	None	None	None	None	N
E/M	0.8897	likely_pathogenic	0.8247	pathogenic	0.426	Stabilizing	None	None	None	None	None	None	None	None	N
E/N	0.8584	likely_pathogenic	0.7968	pathogenic	-0.139	Destabilizing	None	None	None	None	None	None	None	None	N
E/P	0.9931	likely_pathogenic	0.99	pathogenic	-0.094	Destabilizing	None	None	None	None	None	None	None	None	N
E/Q	0.4259	ambiguous	0.3397	benign	-0.097	Destabilizing	None	None	None	None	N	0.446207698	None	None	N
E/R	0.7785	likely_pathogenic	0.6568	pathogenic	0.213	Stabilizing	None	None	None	None	None	None	None	None	N
E/S	0.7552	likely_pathogenic	0.6783	pathogenic	-0.335	Destabilizing	None	None	None	None	None	None	None	None	N
E/T	0.7925	likely_pathogenic	0.7096	pathogenic	-0.154	Destabilizing	None	None	None	None	None	None	None	None	N
E/V	0.7711	likely_pathogenic	0.683	pathogenic	-0.094	Destabilizing	None	None	None	None	N	0.482085845	None	None	N
E/W	0.9951	likely_pathogenic	0.9906	pathogenic	-0.407	Destabilizing	None	None	None	None	None	None	None	None	N
E/Y	0.9651	likely_pathogenic	0.9353	pathogenic	-0.288	Destabilizing	None	None	None	None	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.