TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14744	44455;44456;44457	chr2:178630292;178630291;178630290	chr2:179495019;179495018;179495017
N2AB	13103	39532;39533;39534	chr2:178630292;178630291;178630290	chr2:179495019;179495018;179495017
N2A	12176	36751;36752;36753	chr2:178630292;178630291;178630290	chr2:179495019;179495018;179495017
N2B	5679	17260;17261;17262	chr2:178630292;178630291;178630290	chr2:179495019;179495018;179495017
Novex-1	5804	17635;17636;17637	chr2:178630292;178630291;178630290	chr2:179495019;179495018;179495017
Novex-2	5871	17836;17837;17838	chr2:178630292;178630291;178630290	chr2:179495019;179495018;179495017
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-98
• Domain position: 70
• Structural Position: 154
• Q(SASA): 0.098
• 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/M	rs1465329711	None	0.961	D	0.674	0.274	0.341226946553	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
V/M	rs1465329711	None	0.961	D	0.674	0.274	0.341226946553	gnomAD-4.0.0	2.47987E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.39142E-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	0.8358	likely_pathogenic	0.8641	pathogenic	-2.012	Highly Destabilizing	0.877	D	0.674	prob.neutral	D	0.583414653	None	None	N
V/C	0.972	likely_pathogenic	0.9756	pathogenic	-1.886	Destabilizing	0.999	D	0.713	prob.delet.	None	None	None	None	N
V/D	0.9975	likely_pathogenic	0.9984	pathogenic	-2.351	Highly Destabilizing	0.995	D	0.891	deleterious	None	None	None	None	N
V/E	0.9923	likely_pathogenic	0.9942	pathogenic	-2.067	Highly Destabilizing	0.994	D	0.882	deleterious	D	0.583414653	None	None	N
V/F	0.6607	likely_pathogenic	0.7053	pathogenic	-1.191	Destabilizing	0.971	D	0.759	deleterious	None	None	None	None	N
V/G	0.9281	likely_pathogenic	0.9355	pathogenic	-2.627	Highly Destabilizing	0.994	D	0.903	deleterious	D	0.583414653	None	None	N
V/H	0.9979	likely_pathogenic	0.9983	pathogenic	-2.45	Highly Destabilizing	0.999	D	0.858	deleterious	None	None	None	None	N
V/I	0.0949	likely_benign	0.1113	benign	-0.269	Destabilizing	0.029	N	0.3	neutral	None	None	None	None	N
V/K	0.9946	likely_pathogenic	0.9958	pathogenic	-1.643	Destabilizing	0.985	D	0.883	deleterious	None	None	None	None	N
V/L	0.6103	likely_pathogenic	0.6675	pathogenic	-0.269	Destabilizing	0.022	N	0.361	neutral	D	0.581834925	None	None	N
V/M	0.5588	ambiguous	0.6327	pathogenic	-0.56	Destabilizing	0.961	D	0.674	prob.neutral	D	0.545571647	None	None	N
V/N	0.9923	likely_pathogenic	0.9947	pathogenic	-2.144	Highly Destabilizing	0.995	D	0.904	deleterious	None	None	None	None	N
V/P	0.9949	likely_pathogenic	0.9962	pathogenic	-0.824	Destabilizing	0.995	D	0.874	deleterious	None	None	None	None	N
V/Q	0.9939	likely_pathogenic	0.995	pathogenic	-1.834	Destabilizing	0.995	D	0.883	deleterious	None	None	None	None	N
V/R	0.9886	likely_pathogenic	0.9904	pathogenic	-1.72	Destabilizing	0.995	D	0.908	deleterious	None	None	None	None	N
V/S	0.9701	likely_pathogenic	0.9782	pathogenic	-2.863	Highly Destabilizing	0.985	D	0.875	deleterious	None	None	None	None	N
V/T	0.8875	likely_pathogenic	0.9106	pathogenic	-2.396	Highly Destabilizing	0.904	D	0.677	prob.neutral	None	None	None	None	N
V/W	0.9952	likely_pathogenic	0.9953	pathogenic	-1.661	Destabilizing	0.999	D	0.819	deleterious	None	None	None	None	N
V/Y	0.971	likely_pathogenic	0.9716	pathogenic	-1.267	Destabilizing	0.995	D	0.729	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.