TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18563	55912;55913;55914	chr2:178601310;178601309;178601308	chr2:179466037;179466036;179466035
N2AB	16922	50989;50990;50991	chr2:178601310;178601309;178601308	chr2:179466037;179466036;179466035
N2A	15995	48208;48209;48210	chr2:178601310;178601309;178601308	chr2:179466037;179466036;179466035
N2B	9498	28717;28718;28719	chr2:178601310;178601309;178601308	chr2:179466037;179466036;179466035
Novex-1	9623	29092;29093;29094	chr2:178601310;178601309;178601308	chr2:179466037;179466036;179466035
Novex-2	9690	29293;29294;29295	chr2:178601310;178601309;178601308	chr2:179466037;179466036;179466035
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-22
• Domain position: 85
• Structural Position: 119
• Q(SASA): 0.3482
• 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
P/L	rs1188505019	None	0.709	N	0.724	0.284	0.615969100344	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
P/L	rs1188505019	None	0.709	N	0.724	0.284	0.615969100344	gnomAD-4.0.0	3.12233E-06	None	None	None	None	N	None	4.02145E-05	0	None	0	0	None	0	0	0	0	3.23144E-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
P/A	0.0794	likely_benign	0.0717	benign	-1.265	Destabilizing	0.004	N	0.361	neutral	N	0.511094256	None	None	N
P/C	0.4925	ambiguous	0.4177	ambiguous	-0.738	Destabilizing	0.98	D	0.801	deleterious	None	None	None	None	N
P/D	0.3456	ambiguous	0.3269	benign	-1.245	Destabilizing	0.866	D	0.749	deleterious	None	None	None	None	N
P/E	0.2056	likely_benign	0.193	benign	-1.314	Destabilizing	0.866	D	0.699	prob.neutral	None	None	None	None	N
P/F	0.4412	ambiguous	0.3669	ambiguous	-1.131	Destabilizing	0.98	D	0.803	deleterious	None	None	None	None	N
P/G	0.3229	likely_benign	0.2876	benign	-1.497	Destabilizing	0.48	N	0.664	neutral	None	None	None	None	N
P/H	0.2459	likely_benign	0.213	benign	-1.001	Destabilizing	0.993	D	0.785	deleterious	None	None	None	None	N
P/I	0.2101	likely_benign	0.1969	benign	-0.757	Destabilizing	0.866	D	0.788	deleterious	None	None	None	None	N
P/K	0.2406	likely_benign	0.237	benign	-1.115	Destabilizing	0.866	D	0.701	prob.neutral	None	None	None	None	N
P/L	0.1051	likely_benign	0.0914	benign	-0.757	Destabilizing	0.709	D	0.724	prob.delet.	N	0.519849813	None	None	N
P/M	0.2232	likely_benign	0.2133	benign	-0.521	Destabilizing	0.98	D	0.787	deleterious	None	None	None	None	N
P/N	0.2656	likely_benign	0.2498	benign	-0.787	Destabilizing	0.929	D	0.791	deleterious	None	None	None	None	N
P/Q	0.1405	likely_benign	0.1383	benign	-1.067	Destabilizing	0.908	D	0.785	deleterious	N	0.510190179	None	None	N
P/R	0.2463	likely_benign	0.2165	benign	-0.457	Destabilizing	0.83	D	0.781	deleterious	N	0.515481356	None	None	N
P/S	0.1322	likely_benign	0.1135	benign	-1.175	Destabilizing	0.41	N	0.666	neutral	N	0.476639158	None	None	N
P/T	0.1167	likely_benign	0.11	benign	-1.155	Destabilizing	0.709	D	0.706	prob.neutral	D	0.523639479	None	None	N
P/V	0.1449	likely_benign	0.139	benign	-0.892	Destabilizing	0.764	D	0.7	prob.neutral	None	None	None	None	N
P/W	0.7131	likely_pathogenic	0.6368	pathogenic	-1.233	Destabilizing	0.993	D	0.789	deleterious	None	None	None	None	N
P/Y	0.4419	ambiguous	0.3739	ambiguous	-0.992	Destabilizing	0.98	D	0.802	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.