TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7874	23845;23846;23847	chr2:178720022;178720021;178720020	chr2:179584749;179584748;179584747
N2AB	7557	22894;22895;22896	chr2:178720022;178720021;178720020	chr2:179584749;179584748;179584747
N2A	6630	20113;20114;20115	chr2:178720022;178720021;178720020	chr2:179584749;179584748;179584747
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-63
• Domain position: 80
• Structural Position: 163
• Q(SASA): 0.6297
• 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
A/V	None	None	0.143	N	0.409	0.172	0.362960570912	gnomAD-4.0.0	3.18752E-06	None	None	None	None	I	None	0	0	None	0	2.77793E-05	None	0	0	2.86282E-06	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
A/C	0.8089	likely_pathogenic	0.7685	pathogenic	-0.855	Destabilizing	0.999	D	0.648	neutral	None	None	None	None	I
A/D	0.9385	likely_pathogenic	0.8913	pathogenic	-0.658	Destabilizing	0.983	D	0.675	prob.neutral	D	0.540048909	None	None	I
A/E	0.9002	likely_pathogenic	0.8533	pathogenic	-0.811	Destabilizing	0.991	D	0.583	neutral	None	None	None	None	I
A/F	0.6945	likely_pathogenic	0.6017	pathogenic	-0.96	Destabilizing	0.998	D	0.696	prob.neutral	None	None	None	None	I
A/G	0.3309	likely_benign	0.1991	benign	-0.241	Destabilizing	0.616	D	0.533	neutral	N	0.50609167	None	None	I
A/H	0.9251	likely_pathogenic	0.8856	pathogenic	-0.214	Destabilizing	1.0	D	0.694	prob.neutral	None	None	None	None	I
A/I	0.6907	likely_pathogenic	0.6474	pathogenic	-0.455	Destabilizing	0.993	D	0.581	neutral	None	None	None	None	I
A/K	0.9769	likely_pathogenic	0.9618	pathogenic	-0.561	Destabilizing	0.997	D	0.585	neutral	None	None	None	None	I
A/L	0.6312	likely_pathogenic	0.559	ambiguous	-0.455	Destabilizing	0.976	D	0.551	neutral	None	None	None	None	I
A/M	0.6626	likely_pathogenic	0.5864	pathogenic	-0.576	Destabilizing	1.0	D	0.632	neutral	None	None	None	None	I
A/N	0.8449	likely_pathogenic	0.7494	pathogenic	-0.274	Destabilizing	0.9	D	0.683	prob.neutral	None	None	None	None	I
A/P	0.9799	likely_pathogenic	0.9688	pathogenic	-0.363	Destabilizing	0.992	D	0.612	neutral	D	0.551405214	None	None	I
A/Q	0.8898	likely_pathogenic	0.8474	pathogenic	-0.553	Destabilizing	0.998	D	0.634	neutral	None	None	None	None	I
A/R	0.9243	likely_pathogenic	0.8975	pathogenic	-0.104	Destabilizing	0.998	D	0.629	neutral	None	None	None	None	I
A/S	0.1902	likely_benign	0.1507	benign	-0.44	Destabilizing	0.099	N	0.405	neutral	N	0.512826393	None	None	I
A/T	0.3604	ambiguous	0.3005	benign	-0.525	Destabilizing	0.844	D	0.579	neutral	D	0.52539724	None	None	I
A/V	0.347	ambiguous	0.3135	benign	-0.363	Destabilizing	0.143	N	0.409	neutral	N	0.491538209	None	None	I
A/W	0.9708	likely_pathogenic	0.9541	pathogenic	-1.046	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	I
A/Y	0.8892	likely_pathogenic	0.8332	pathogenic	-0.74	Destabilizing	0.999	D	0.698	prob.neutral	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.