TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3052	9379;9380;9381	chr2:178768682;178768681;178768680	chr2:179633409;179633408;179633407
N2AB	3052	9379;9380;9381	chr2:178768682;178768681;178768680	chr2:179633409;179633408;179633407
N2A	3052	9379;9380;9381	chr2:178768682;178768681;178768680	chr2:179633409;179633408;179633407
N2B	3006	9241;9242;9243	chr2:178768682;178768681;178768680	chr2:179633409;179633408;179633407
Novex-1	3006	9241;9242;9243	chr2:178768682;178768681;178768680	chr2:179633409;179633408;179633407
Novex-2	3006	9241;9242;9243	chr2:178768682;178768681;178768680	chr2:179633409;179633408;179633407
Novex-3	3052	9379;9380;9381	chr2:178768682;178768681;178768680	chr2:179633409;179633408;179633407

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Ig-20
• Domain position: 84
• Structural Position: 175
• Q(SASA): 0.2507
• 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	rs763833161	-0.35	0.003	N	0.151	0.08	0.1749357433	gnomAD-2.1.1	3.58E-05	None	None	None	None	N	None	0	2.31468E-04	None	0	0	None	0	None	0	8.81E-06	0
Y/H	rs763833161	-0.35	0.003	N	0.151	0.08	0.1749357433	gnomAD-4.0.0	1.64183E-05	None	None	None	None	N	None	0	2.01279E-04	None	0	0	None	0	0	1.34895E-05	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	0.9038	likely_pathogenic	0.8309	pathogenic	-1.7	Destabilizing	0.388	N	0.409	neutral	None	None	None	None	N
Y/C	0.5388	ambiguous	0.4507	ambiguous	-0.217	Destabilizing	0.975	D	0.441	neutral	N	0.334453496	None	None	N
Y/D	0.8898	likely_pathogenic	0.7743	pathogenic	-0.012	Destabilizing	0.627	D	0.447	neutral	N	0.343856911	None	None	N
Y/E	0.9548	likely_pathogenic	0.9017	pathogenic	0.001	Stabilizing	0.69	D	0.425	neutral	None	None	None	None	N
Y/F	0.0979	likely_benign	0.0945	benign	-0.946	Destabilizing	0.001	N	0.127	neutral	N	0.33888026	None	None	N
Y/G	0.9221	likely_pathogenic	0.8578	pathogenic	-1.958	Destabilizing	0.388	N	0.427	neutral	None	None	None	None	N
Y/H	0.5196	ambiguous	0.2968	benign	-0.571	Destabilizing	0.003	N	0.151	neutral	N	0.343856911	None	None	N
Y/I	0.7545	likely_pathogenic	0.6587	pathogenic	-0.97	Destabilizing	0.241	N	0.413	neutral	None	None	None	None	N
Y/K	0.9173	likely_pathogenic	0.8403	pathogenic	-0.414	Destabilizing	0.69	D	0.433	neutral	None	None	None	None	N
Y/L	0.7161	likely_pathogenic	0.6151	pathogenic	-0.97	Destabilizing	0.116	N	0.415	neutral	None	None	None	None	N
Y/M	0.8163	likely_pathogenic	0.7491	pathogenic	-0.502	Destabilizing	0.818	D	0.409	neutral	None	None	None	None	N
Y/N	0.6899	likely_pathogenic	0.498	ambiguous	-0.5	Destabilizing	0.627	D	0.441	neutral	N	0.350423176	None	None	N
Y/P	0.9944	likely_pathogenic	0.9894	pathogenic	-1.2	Destabilizing	0.932	D	0.454	neutral	None	None	None	None	N
Y/Q	0.9052	likely_pathogenic	0.8002	pathogenic	-0.544	Destabilizing	0.69	D	0.436	neutral	None	None	None	None	N
Y/R	0.8173	likely_pathogenic	0.6893	pathogenic	0.068	Stabilizing	0.69	D	0.462	neutral	None	None	None	None	N
Y/S	0.7464	likely_pathogenic	0.5641	pathogenic	-1.018	Destabilizing	0.324	N	0.423	neutral	N	0.346494136	None	None	N
Y/T	0.8302	likely_pathogenic	0.698	pathogenic	-0.915	Destabilizing	0.818	D	0.424	neutral	None	None	None	None	N
Y/V	0.6861	likely_pathogenic	0.5741	pathogenic	-1.2	Destabilizing	0.241	N	0.386	neutral	None	None	None	None	N
Y/W	0.6448	likely_pathogenic	0.5802	pathogenic	-0.777	Destabilizing	0.932	D	0.441	neutral	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.