TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19777	59554;59555;59556	chr2:178592790;178592789;178592788	chr2:179457517;179457516;179457515
N2AB	18136	54631;54632;54633	chr2:178592790;178592789;178592788	chr2:179457517;179457516;179457515
N2A	17209	51850;51851;51852	chr2:178592790;178592789;178592788	chr2:179457517;179457516;179457515
N2B	10712	32359;32360;32361	chr2:178592790;178592789;178592788	chr2:179457517;179457516;179457515
Novex-1	10837	32734;32735;32736	chr2:178592790;178592789;178592788	chr2:179457517;179457516;179457515
Novex-2	10904	32935;32936;32937	chr2:178592790;178592789;178592788	chr2:179457517;179457516;179457515
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Fn3-31
• Domain position: 98
• Structural Position: 130
• Q(SASA): 0.0506
• 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
V/I	rs1178263259	None	0.051	N	0.309	0.14	0.483596354421	gnomAD-4.0.0	2.05309E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69876E-06	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
V/A	0.3783	ambiguous	0.3759	ambiguous	-2.326	Highly Destabilizing	0.005	N	0.305	neutral	N	0.43805044	None	None	N
V/C	0.8586	likely_pathogenic	0.8593	pathogenic	-2.533	Highly Destabilizing	0.998	D	0.696	prob.delet.	None	None	None	None	N
V/D	0.9917	likely_pathogenic	0.991	pathogenic	-3.515	Highly Destabilizing	0.974	D	0.817	deleterious	None	None	None	None	N
V/E	0.9767	likely_pathogenic	0.9747	pathogenic	-3.3	Highly Destabilizing	0.933	D	0.733	deleterious	N	0.507470796	None	None	N
V/F	0.8992	likely_pathogenic	0.892	pathogenic	-1.278	Destabilizing	0.974	D	0.709	prob.delet.	None	None	None	None	N
V/G	0.7296	likely_pathogenic	0.7314	pathogenic	-2.796	Highly Destabilizing	0.666	D	0.776	deleterious	N	0.517559653	None	None	N
V/H	0.994	likely_pathogenic	0.9929	pathogenic	-2.354	Highly Destabilizing	0.998	D	0.804	deleterious	None	None	None	None	N
V/I	0.163	likely_benign	0.1458	benign	-0.994	Destabilizing	0.051	N	0.309	neutral	N	0.486129602	None	None	N
V/K	0.9833	likely_pathogenic	0.9822	pathogenic	-1.932	Destabilizing	0.949	D	0.743	deleterious	None	None	None	None	N
V/L	0.5752	likely_pathogenic	0.5821	pathogenic	-0.994	Destabilizing	0.451	N	0.518	neutral	N	0.492819126	None	None	N
V/M	0.6801	likely_pathogenic	0.6678	pathogenic	-1.5	Destabilizing	0.974	D	0.616	neutral	None	None	None	None	N
V/N	0.9584	likely_pathogenic	0.954	pathogenic	-2.453	Highly Destabilizing	0.974	D	0.807	deleterious	None	None	None	None	N
V/P	0.6027	likely_pathogenic	0.58	pathogenic	-1.417	Destabilizing	0.974	D	0.767	deleterious	None	None	None	None	N
V/Q	0.9652	likely_pathogenic	0.9627	pathogenic	-2.296	Highly Destabilizing	0.974	D	0.757	deleterious	None	None	None	None	N
V/R	0.9657	likely_pathogenic	0.9641	pathogenic	-1.745	Destabilizing	0.974	D	0.811	deleterious	None	None	None	None	N
V/S	0.7902	likely_pathogenic	0.7792	pathogenic	-2.94	Highly Destabilizing	0.725	D	0.72	deleterious	None	None	None	None	N
V/T	0.6976	likely_pathogenic	0.682	pathogenic	-2.596	Highly Destabilizing	0.841	D	0.583	neutral	None	None	None	None	N
V/W	0.9981	likely_pathogenic	0.9975	pathogenic	-1.739	Destabilizing	0.998	D	0.743	deleterious	None	None	None	None	N
V/Y	0.9914	likely_pathogenic	0.9899	pathogenic	-1.496	Destabilizing	0.991	D	0.683	prob.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.