TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34196	102811;102812;102813	chr2:178534029;178534028;178534027	chr2:179398756;179398755;179398754
N2AB	32555	97888;97889;97890	chr2:178534029;178534028;178534027	chr2:179398756;179398755;179398754
N2A	31628	95107;95108;95109	chr2:178534029;178534028;178534027	chr2:179398756;179398755;179398754
N2B	25131	75616;75617;75618	chr2:178534029;178534028;178534027	chr2:179398756;179398755;179398754
Novex-1	25256	75991;75992;75993	chr2:178534029;178534028;178534027	chr2:179398756;179398755;179398754
Novex-2	25323	76192;76193;76194	chr2:178534029;178534028;178534027	chr2:179398756;179398755;179398754
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-160
• Domain position: 60
• Structural Position: 140
• Q(SASA): 0.1069
• 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	rs1185169765	None	None	N	0.255	0.099	0.110078149338	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
V/I	rs1185169765	None	None	N	0.255	0.099	0.110078149338	gnomAD-4.0.0	2.47856E-06	None	None	None	None	N	None	1.33479E-05	0	None	0	0	None	0	0	2.54264E-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	0.7502	likely_pathogenic	0.7123	pathogenic	-2.615	Highly Destabilizing	0.104	N	0.639	neutral	N	0.491963888	None	None	N
V/C	0.9154	likely_pathogenic	0.905	pathogenic	-1.846	Destabilizing	0.968	D	0.808	deleterious	None	None	None	None	N
V/D	0.973	likely_pathogenic	0.9609	pathogenic	-3.341	Highly Destabilizing	0.667	D	0.897	deleterious	N	0.492724357	None	None	N
V/E	0.9365	likely_pathogenic	0.9133	pathogenic	-3.047	Highly Destabilizing	0.726	D	0.863	deleterious	None	None	None	None	N
V/F	0.5592	ambiguous	0.5215	ambiguous	-1.594	Destabilizing	0.331	N	0.789	deleterious	N	0.481593361	None	None	N
V/G	0.8417	likely_pathogenic	0.8037	pathogenic	-3.134	Highly Destabilizing	0.667	D	0.868	deleterious	N	0.492724357	None	None	N
V/H	0.9701	likely_pathogenic	0.9571	pathogenic	-2.907	Highly Destabilizing	0.968	D	0.889	deleterious	None	None	None	None	N
V/I	0.0778	likely_benign	0.0799	benign	-1.062	Destabilizing	None	N	0.255	neutral	N	0.367749701	None	None	N
V/K	0.9347	likely_pathogenic	0.9099	pathogenic	-2.184	Highly Destabilizing	0.726	D	0.861	deleterious	None	None	None	None	N
V/L	0.3235	likely_benign	0.2959	benign	-1.062	Destabilizing	None	N	0.337	neutral	N	0.46148466	None	None	N
V/M	0.3568	ambiguous	0.3221	benign	-1.333	Destabilizing	0.396	N	0.695	prob.neutral	None	None	None	None	N
V/N	0.9204	likely_pathogenic	0.8908	pathogenic	-2.906	Highly Destabilizing	0.89	D	0.888	deleterious	None	None	None	None	N
V/P	0.9815	likely_pathogenic	0.9784	pathogenic	-1.57	Destabilizing	0.89	D	0.875	deleterious	None	None	None	None	N
V/Q	0.9224	likely_pathogenic	0.8887	pathogenic	-2.542	Highly Destabilizing	0.89	D	0.881	deleterious	None	None	None	None	N
V/R	0.917	likely_pathogenic	0.8776	pathogenic	-2.278	Highly Destabilizing	0.726	D	0.889	deleterious	None	None	None	None	N
V/S	0.8741	likely_pathogenic	0.8381	pathogenic	-3.269	Highly Destabilizing	0.726	D	0.833	deleterious	None	None	None	None	N
V/T	0.8066	likely_pathogenic	0.7855	pathogenic	-2.837	Highly Destabilizing	0.272	N	0.66	neutral	None	None	None	None	N
V/W	0.9862	likely_pathogenic	0.9818	pathogenic	-1.958	Destabilizing	0.968	D	0.887	deleterious	None	None	None	None	N
V/Y	0.9363	likely_pathogenic	0.92	pathogenic	-1.84	Destabilizing	0.726	D	0.805	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.