TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22228	66907;66908;66909	chr2:178581586;178581585;178581584	chr2:179446313;179446312;179446311
N2AB	20587	61984;61985;61986	chr2:178581586;178581585;178581584	chr2:179446313;179446312;179446311
N2A	19660	59203;59204;59205	chr2:178581586;178581585;178581584	chr2:179446313;179446312;179446311
N2B	13163	39712;39713;39714	chr2:178581586;178581585;178581584	chr2:179446313;179446312;179446311
Novex-1	13288	40087;40088;40089	chr2:178581586;178581585;178581584	chr2:179446313;179446312;179446311
Novex-2	13355	40288;40289;40290	chr2:178581586;178581585;178581584	chr2:179446313;179446312;179446311
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: Fn3-49
• Domain position: 73
• Structural Position: 104
• Q(SASA): 0.1001
• 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
Y/H	rs1170889599	-2.211	1.0	D	0.853	0.838	0.840859371154	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	5.63E-05	None	0	None	0	0	0
Y/H	rs1170889599	-2.211	1.0	D	0.853	0.838	0.840859371154	gnomAD-4.0.0	1.59384E-06	None	None	None	None	N	None	0	0	None	0	2.78722E-05	None	0	0	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
Y/A	0.996	likely_pathogenic	0.997	pathogenic	-3.067	Highly Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	N
Y/C	0.943	likely_pathogenic	0.9557	pathogenic	-1.698	Destabilizing	1.0	D	0.89	deleterious	D	0.654594887	None	None	N
Y/D	0.9971	likely_pathogenic	0.9975	pathogenic	-3.784	Highly Destabilizing	1.0	D	0.908	deleterious	D	0.686865774	None	None	N
Y/E	0.9987	likely_pathogenic	0.9989	pathogenic	-3.561	Highly Destabilizing	1.0	D	0.912	deleterious	None	None	None	None	N
Y/F	0.4334	ambiguous	0.4391	ambiguous	-1.195	Destabilizing	0.999	D	0.769	deleterious	D	0.619114774	None	None	N
Y/G	0.9861	likely_pathogenic	0.989	pathogenic	-3.484	Highly Destabilizing	1.0	D	0.913	deleterious	None	None	None	None	N
Y/H	0.9797	likely_pathogenic	0.9822	pathogenic	-2.347	Highly Destabilizing	1.0	D	0.853	deleterious	D	0.686865774	None	None	N
Y/I	0.98	likely_pathogenic	0.9831	pathogenic	-1.662	Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
Y/K	0.9988	likely_pathogenic	0.9991	pathogenic	-2.448	Highly Destabilizing	1.0	D	0.908	deleterious	None	None	None	None	N
Y/L	0.9554	likely_pathogenic	0.9608	pathogenic	-1.662	Destabilizing	0.999	D	0.834	deleterious	None	None	None	None	N
Y/M	0.9885	likely_pathogenic	0.9908	pathogenic	-1.363	Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	N
Y/N	0.9789	likely_pathogenic	0.9832	pathogenic	-3.361	Highly Destabilizing	1.0	D	0.899	deleterious	D	0.686663969	None	None	N
Y/P	0.999	likely_pathogenic	0.9991	pathogenic	-2.149	Highly Destabilizing	1.0	D	0.926	deleterious	None	None	None	None	N
Y/Q	0.9978	likely_pathogenic	0.9984	pathogenic	-3.039	Highly Destabilizing	1.0	D	0.868	deleterious	None	None	None	None	N
Y/R	0.9959	likely_pathogenic	0.9969	pathogenic	-2.349	Highly Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
Y/S	0.99	likely_pathogenic	0.9919	pathogenic	-3.592	Highly Destabilizing	1.0	D	0.912	deleterious	D	0.686865774	None	None	N
Y/T	0.9967	likely_pathogenic	0.9974	pathogenic	-3.244	Highly Destabilizing	1.0	D	0.913	deleterious	None	None	None	None	N
Y/V	0.9591	likely_pathogenic	0.9667	pathogenic	-2.149	Highly Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
Y/W	0.8916	likely_pathogenic	0.9004	pathogenic	-0.533	Destabilizing	1.0	D	0.837	deleterious	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.