TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21993	66202;66203;66204	chr2:178582479;178582478;178582477	chr2:179447206;179447205;179447204
N2AB	20352	61279;61280;61281	chr2:178582479;178582478;178582477	chr2:179447206;179447205;179447204
N2A	19425	58498;58499;58500	chr2:178582479;178582478;178582477	chr2:179447206;179447205;179447204
N2B	12928	39007;39008;39009	chr2:178582479;178582478;178582477	chr2:179447206;179447205;179447204
Novex-1	13053	39382;39383;39384	chr2:178582479;178582478;178582477	chr2:179447206;179447205;179447204
Novex-2	13120	39583;39584;39585	chr2:178582479;178582478;178582477	chr2:179447206;179447205;179447204
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-47
• Domain position: 38
• Structural Position: 40
• Q(SASA): 0.1109
• 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/A	rs1483586965	None	0.104	D	0.573	0.462	0.656662538205	gnomAD-4.0.0	1.59318E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86136E-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	0.9182	likely_pathogenic	0.8719	pathogenic	-2.46	Highly Destabilizing	0.104	N	0.573	neutral	D	0.530614707	None	None	N
V/C	0.9816	likely_pathogenic	0.972	pathogenic	-2.14	Highly Destabilizing	0.968	D	0.783	deleterious	None	None	None	None	N
V/D	0.9996	likely_pathogenic	0.9993	pathogenic	-3.499	Highly Destabilizing	0.667	D	0.873	deleterious	D	0.554087786	None	None	N
V/E	0.998	likely_pathogenic	0.9968	pathogenic	-3.202	Highly Destabilizing	0.726	D	0.809	deleterious	None	None	None	None	N
V/F	0.9434	likely_pathogenic	0.9278	pathogenic	-1.396	Destabilizing	0.497	N	0.709	prob.delet.	D	0.542477991	None	None	N
V/G	0.9859	likely_pathogenic	0.9805	pathogenic	-3.061	Highly Destabilizing	0.667	D	0.837	deleterious	D	0.554087786	None	None	N
V/H	0.9993	likely_pathogenic	0.999	pathogenic	-2.941	Highly Destabilizing	0.968	D	0.877	deleterious	None	None	None	None	N
V/I	0.0733	likely_benign	0.0733	benign	-0.724	Destabilizing	None	N	0.152	neutral	N	0.475002957	None	None	N
V/K	0.9977	likely_pathogenic	0.9968	pathogenic	-2.127	Highly Destabilizing	0.726	D	0.811	deleterious	None	None	None	None	N
V/L	0.5998	likely_pathogenic	0.4868	ambiguous	-0.724	Destabilizing	None	N	0.298	neutral	N	0.485358811	None	None	N
V/M	0.8032	likely_pathogenic	0.7426	pathogenic	-1.003	Destabilizing	0.567	D	0.635	neutral	None	None	None	None	N
V/N	0.9986	likely_pathogenic	0.9978	pathogenic	-2.73	Highly Destabilizing	0.89	D	0.878	deleterious	None	None	None	None	N
V/P	0.9979	likely_pathogenic	0.9958	pathogenic	-1.282	Destabilizing	0.89	D	0.849	deleterious	None	None	None	None	N
V/Q	0.9972	likely_pathogenic	0.9961	pathogenic	-2.421	Highly Destabilizing	0.89	D	0.871	deleterious	None	None	None	None	N
V/R	0.9952	likely_pathogenic	0.9932	pathogenic	-2.097	Highly Destabilizing	0.726	D	0.876	deleterious	None	None	None	None	N
V/S	0.9908	likely_pathogenic	0.9852	pathogenic	-3.281	Highly Destabilizing	0.726	D	0.762	deleterious	None	None	None	None	N
V/T	0.9324	likely_pathogenic	0.8894	pathogenic	-2.83	Highly Destabilizing	0.272	N	0.585	neutral	None	None	None	None	N
V/W	0.9989	likely_pathogenic	0.9984	pathogenic	-2.029	Highly Destabilizing	0.968	D	0.859	deleterious	None	None	None	None	N
V/Y	0.9967	likely_pathogenic	0.9954	pathogenic	-1.697	Destabilizing	0.726	D	0.745	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.