TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23435	70528;70529;70530	chr2:178575829;178575828;178575827	chr2:179440556;179440555;179440554
N2AB	21794	65605;65606;65607	chr2:178575829;178575828;178575827	chr2:179440556;179440555;179440554
N2A	20867	62824;62825;62826	chr2:178575829;178575828;178575827	chr2:179440556;179440555;179440554
N2B	14370	43333;43334;43335	chr2:178575829;178575828;178575827	chr2:179440556;179440555;179440554
Novex-1	14495	43708;43709;43710	chr2:178575829;178575828;178575827	chr2:179440556;179440555;179440554
Novex-2	14562	43909;43910;43911	chr2:178575829;178575828;178575827	chr2:179440556;179440555;179440554
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACG
• RefSeq wild type template codon: TGC
• Domain: Fn3-58
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.4275
• 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
T/K	None	None	0.893	N	0.561	0.354	0.277317399466	gnomAD-4.0.0	2.05297E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.69883E-06	0	0
T/M	rs1324845938	None	0.793	N	0.521	0.414	0.423836183345	gnomAD-4.0.0	8.89624E-06	None	None	None	None	I	None	2.98918E-05	2.23624E-05	None	0	2.52169E-05	None	0	0	7.19689E-06	1.15955E-05	1.65684E-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
T/A	0.221	likely_benign	0.2952	benign	-0.813	Destabilizing	0.045	N	0.403	neutral	N	0.486355236	None	None	I
T/C	0.6496	likely_pathogenic	0.734	pathogenic	-0.472	Destabilizing	0.996	D	0.565	neutral	None	None	None	None	I
T/D	0.9202	likely_pathogenic	0.9503	pathogenic	-0.078	Destabilizing	0.767	D	0.509	neutral	None	None	None	None	I
T/E	0.8535	likely_pathogenic	0.9044	pathogenic	-0.139	Destabilizing	0.757	D	0.547	neutral	None	None	None	None	I
T/F	0.8243	likely_pathogenic	0.8875	pathogenic	-1.236	Destabilizing	0.976	D	0.791	deleterious	None	None	None	None	I
T/G	0.5745	likely_pathogenic	0.6591	pathogenic	-0.963	Destabilizing	0.797	D	0.59	neutral	None	None	None	None	I
T/H	0.6691	likely_pathogenic	0.7543	pathogenic	-1.329	Destabilizing	0.997	D	0.762	deleterious	None	None	None	None	I
T/I	0.6284	likely_pathogenic	0.7123	pathogenic	-0.523	Destabilizing	0.885	D	0.501	neutral	None	None	None	None	I
T/K	0.618	likely_pathogenic	0.7126	pathogenic	-0.528	Destabilizing	0.893	D	0.561	neutral	N	0.459072634	None	None	I
T/L	0.4484	ambiguous	0.5247	ambiguous	-0.523	Destabilizing	0.429	N	0.465	neutral	None	None	None	None	I
T/M	0.2779	likely_benign	0.3442	ambiguous	-0.063	Destabilizing	0.793	D	0.521	neutral	N	0.482252612	None	None	I
T/N	0.4727	ambiguous	0.5748	pathogenic	-0.335	Destabilizing	0.767	D	0.458	neutral	None	None	None	None	I
T/P	0.505	ambiguous	0.5788	pathogenic	-0.592	Destabilizing	0.834	D	0.551	neutral	N	0.490835549	None	None	I
T/Q	0.6388	likely_pathogenic	0.723	pathogenic	-0.668	Destabilizing	0.936	D	0.567	neutral	None	None	None	None	I
T/R	0.6026	likely_pathogenic	0.7028	pathogenic	-0.221	Destabilizing	0.987	D	0.553	neutral	N	0.468481551	None	None	I
T/S	0.1434	likely_benign	0.1883	benign	-0.624	Destabilizing	0.003	N	0.185	neutral	N	0.442932532	None	None	I
T/V	0.4072	ambiguous	0.4802	ambiguous	-0.592	Destabilizing	0.61	D	0.388	neutral	None	None	None	None	I
T/W	0.9652	likely_pathogenic	0.9785	pathogenic	-1.113	Destabilizing	0.999	D	0.81	deleterious	None	None	None	None	I
T/Y	0.7922	likely_pathogenic	0.856	pathogenic	-0.877	Destabilizing	0.988	D	0.799	deleterious	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.