TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27648	83167;83168;83169	chr2:178563190;178563189;178563188	chr2:179427917;179427916;179427915
N2AB	26007	78244;78245;78246	chr2:178563190;178563189;178563188	chr2:179427917;179427916;179427915
N2A	25080	75463;75464;75465	chr2:178563190;178563189;178563188	chr2:179427917;179427916;179427915
N2B	18583	55972;55973;55974	chr2:178563190;178563189;178563188	chr2:179427917;179427916;179427915
Novex-1	18708	56347;56348;56349	chr2:178563190;178563189;178563188	chr2:179427917;179427916;179427915
Novex-2	18775	56548;56549;56550	chr2:178563190;178563189;178563188	chr2:179427917;179427916;179427915
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Fn3-89
• Domain position: 79
• Structural Position: 110
• Q(SASA): 0.0953
• 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
A/P	None	None	1.0	D	0.831	0.864	0.658139403113	gnomAD-4.0.0	1.59137E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43271E-05	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
A/C	0.8496	likely_pathogenic	0.8579	pathogenic	-1.818	Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	N
A/D	0.9971	likely_pathogenic	0.9971	pathogenic	-2.992	Highly Destabilizing	1.0	D	0.801	deleterious	D	0.660097245	None	None	N
A/E	0.9959	likely_pathogenic	0.9959	pathogenic	-2.783	Highly Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
A/F	0.9884	likely_pathogenic	0.9889	pathogenic	-0.73	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
A/G	0.468	ambiguous	0.4048	ambiguous	-2.007	Highly Destabilizing	1.0	D	0.631	neutral	D	0.602763294	None	None	N
A/H	0.9958	likely_pathogenic	0.9962	pathogenic	-1.988	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
A/I	0.9766	likely_pathogenic	0.9757	pathogenic	-0.412	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
A/K	0.999	likely_pathogenic	0.999	pathogenic	-1.402	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
A/L	0.9166	likely_pathogenic	0.914	pathogenic	-0.412	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
A/M	0.9628	likely_pathogenic	0.9655	pathogenic	-0.993	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
A/N	0.9879	likely_pathogenic	0.9891	pathogenic	-1.838	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
A/P	0.9691	likely_pathogenic	0.9653	pathogenic	-0.766	Destabilizing	1.0	D	0.831	deleterious	D	0.611201584	None	None	N
A/Q	0.9884	likely_pathogenic	0.9893	pathogenic	-1.631	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
A/R	0.9937	likely_pathogenic	0.9937	pathogenic	-1.442	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
A/S	0.2851	likely_benign	0.2887	benign	-2.177	Highly Destabilizing	1.0	D	0.62	neutral	D	0.593567789	None	None	N
A/T	0.7996	likely_pathogenic	0.8061	pathogenic	-1.861	Destabilizing	1.0	D	0.776	deleterious	D	0.659088223	None	None	N
A/V	0.8824	likely_pathogenic	0.8783	pathogenic	-0.766	Destabilizing	1.0	D	0.695	prob.neutral	D	0.642463449	None	None	N
A/W	0.9988	likely_pathogenic	0.9988	pathogenic	-1.38	Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	N
A/Y	0.9955	likely_pathogenic	0.996	pathogenic	-1.005	Destabilizing	1.0	D	0.85	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.