TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24889	74890;74891;74892	chr2:178571467;178571466;178571465	chr2:179436194;179436193;179436192
N2AB	23248	69967;69968;69969	chr2:178571467;178571466;178571465	chr2:179436194;179436193;179436192
N2A	22321	67186;67187;67188	chr2:178571467;178571466;178571465	chr2:179436194;179436193;179436192
N2B	15824	47695;47696;47697	chr2:178571467;178571466;178571465	chr2:179436194;179436193;179436192
Novex-1	15949	48070;48071;48072	chr2:178571467;178571466;178571465	chr2:179436194;179436193;179436192
Novex-2	16016	48271;48272;48273	chr2:178571467;178571466;178571465	chr2:179436194;179436193;179436192
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-68
• Domain position: 82
• Structural Position: 114
• Q(SASA): 0.7554
• 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
Y/C	rs368931248	0.147	0.999	N	0.68	0.413	None	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.92E-06	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
Y/A	0.9824	likely_pathogenic	0.9854	pathogenic	-0.749	Destabilizing	0.916	D	0.629	neutral	None	None	None	None	I
Y/C	0.723	likely_pathogenic	0.7784	pathogenic	0.035	Stabilizing	0.999	D	0.68	prob.neutral	N	0.517537439	None	None	I
Y/D	0.9815	likely_pathogenic	0.9838	pathogenic	0.942	Stabilizing	0.994	D	0.664	neutral	N	0.489229096	None	None	I
Y/E	0.9953	likely_pathogenic	0.9957	pathogenic	0.926	Stabilizing	0.987	D	0.643	neutral	None	None	None	None	I
Y/F	0.1289	likely_benign	0.1283	benign	-0.372	Destabilizing	0.892	D	0.558	neutral	N	0.460529363	None	None	I
Y/G	0.9708	likely_pathogenic	0.9762	pathogenic	-0.938	Destabilizing	0.987	D	0.643	neutral	None	None	None	None	I
Y/H	0.7992	likely_pathogenic	0.8415	pathogenic	0.209	Stabilizing	0.994	D	0.614	neutral	N	0.464986002	None	None	I
Y/I	0.9312	likely_pathogenic	0.9295	pathogenic	-0.274	Destabilizing	0.95	D	0.606	neutral	None	None	None	None	I
Y/K	0.9894	likely_pathogenic	0.9915	pathogenic	0.171	Stabilizing	0.975	D	0.634	neutral	None	None	None	None	I
Y/L	0.8955	likely_pathogenic	0.8987	pathogenic	-0.274	Destabilizing	0.437	N	0.601	neutral	None	None	None	None	I
Y/M	0.9486	likely_pathogenic	0.951	pathogenic	-0.129	Destabilizing	0.693	D	0.557	neutral	None	None	None	None	I
Y/N	0.9044	likely_pathogenic	0.9217	pathogenic	-0.03	Destabilizing	0.983	D	0.651	neutral	N	0.470226241	None	None	I
Y/P	0.9974	likely_pathogenic	0.9977	pathogenic	-0.413	Destabilizing	0.996	D	0.683	prob.neutral	None	None	None	None	I
Y/Q	0.9851	likely_pathogenic	0.9879	pathogenic	0.01	Stabilizing	0.987	D	0.615	neutral	None	None	None	None	I
Y/R	0.9693	likely_pathogenic	0.9751	pathogenic	0.454	Stabilizing	0.987	D	0.652	neutral	None	None	None	None	I
Y/S	0.9485	likely_pathogenic	0.9585	pathogenic	-0.496	Destabilizing	0.967	D	0.589	neutral	N	0.468517948	None	None	I
Y/T	0.9859	likely_pathogenic	0.9877	pathogenic	-0.42	Destabilizing	0.975	D	0.623	neutral	None	None	None	None	I
Y/V	0.9059	likely_pathogenic	0.9117	pathogenic	-0.413	Destabilizing	0.845	D	0.643	neutral	None	None	None	None	I
Y/W	0.6782	likely_pathogenic	0.6958	pathogenic	-0.459	Destabilizing	0.999	D	0.599	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.