TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26105	78538;78539;78540	chr2:178567819;178567818;178567817	chr2:179432546;179432545;179432544
N2AB	24464	73615;73616;73617	chr2:178567819;178567818;178567817	chr2:179432546;179432545;179432544
N2A	23537	70834;70835;70836	chr2:178567819;178567818;178567817	chr2:179432546;179432545;179432544
N2B	17040	51343;51344;51345	chr2:178567819;178567818;178567817	chr2:179432546;179432545;179432544
Novex-1	17165	51718;51719;51720	chr2:178567819;178567818;178567817	chr2:179432546;179432545;179432544
Novex-2	17232	51919;51920;51921	chr2:178567819;178567818;178567817	chr2:179432546;179432545;179432544
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Fn3-78
• Domain position: 18
• Structural Position: 20
• Q(SASA): 0.0882
• 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
I/T	None	None	0.896	N	0.761	0.385	0.555867075214	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
I/A	0.8926	likely_pathogenic	0.8907	pathogenic	-2.958	Highly Destabilizing	0.702	D	0.685	prob.neutral	None	None	None	None	N
I/C	0.9208	likely_pathogenic	0.9169	pathogenic	-2.298	Highly Destabilizing	0.999	D	0.789	deleterious	None	None	None	None	N
I/D	0.9985	likely_pathogenic	0.9979	pathogenic	-3.453	Highly Destabilizing	0.996	D	0.83	deleterious	None	None	None	None	N
I/E	0.9956	likely_pathogenic	0.9945	pathogenic	-3.12	Highly Destabilizing	0.988	D	0.811	deleterious	None	None	None	None	N
I/F	0.7457	likely_pathogenic	0.7478	pathogenic	-1.697	Destabilizing	0.984	D	0.709	prob.delet.	N	0.471584778	None	None	N
I/G	0.9886	likely_pathogenic	0.9875	pathogenic	-3.591	Highly Destabilizing	0.988	D	0.791	deleterious	None	None	None	None	N
I/H	0.9959	likely_pathogenic	0.9954	pathogenic	-3.175	Highly Destabilizing	0.999	D	0.802	deleterious	None	None	None	None	N
I/K	0.9935	likely_pathogenic	0.992	pathogenic	-2.137	Highly Destabilizing	0.988	D	0.813	deleterious	None	None	None	None	N
I/L	0.3831	ambiguous	0.3869	ambiguous	-1.049	Destabilizing	0.437	N	0.407	neutral	N	0.463673164	None	None	N
I/M	0.3216	likely_benign	0.3216	benign	-1.363	Destabilizing	0.984	D	0.661	neutral	N	0.487168886	None	None	N
I/N	0.9779	likely_pathogenic	0.9694	pathogenic	-2.837	Highly Destabilizing	0.995	D	0.824	deleterious	N	0.499096782	None	None	N
I/P	0.998	likely_pathogenic	0.9977	pathogenic	-1.677	Destabilizing	0.996	D	0.832	deleterious	None	None	None	None	N
I/Q	0.9932	likely_pathogenic	0.9922	pathogenic	-2.478	Highly Destabilizing	0.996	D	0.827	deleterious	None	None	None	None	N
I/R	0.9897	likely_pathogenic	0.988	pathogenic	-2.183	Highly Destabilizing	0.996	D	0.823	deleterious	None	None	None	None	N
I/S	0.9603	likely_pathogenic	0.9512	pathogenic	-3.467	Highly Destabilizing	0.984	D	0.783	deleterious	N	0.476130681	None	None	N
I/T	0.91	likely_pathogenic	0.9019	pathogenic	-2.96	Highly Destabilizing	0.896	D	0.761	deleterious	N	0.472091757	None	None	N
I/V	0.0945	likely_benign	0.0968	benign	-1.677	Destabilizing	0.004	N	0.181	neutral	N	0.347344639	None	None	N
I/W	0.9952	likely_pathogenic	0.9957	pathogenic	-2.035	Highly Destabilizing	0.999	D	0.793	deleterious	None	None	None	None	N
I/Y	0.9727	likely_pathogenic	0.9705	pathogenic	-1.871	Destabilizing	0.996	D	0.829	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.