TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6296	19111;19112;19113	chr2:178729152;178729151;178729150	chr2:179593879;179593878;179593877
N2AB	5979	18160;18161;18162	chr2:178729152;178729151;178729150	chr2:179593879;179593878;179593877
N2A	5052	15379;15380;15381	chr2:178729152;178729151;178729150	chr2:179593879;179593878;179593877
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-47
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.6255
• Predicted PPI site: I

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
K/E	None	None	0.016	N	0.139	0.262	0.309839678437	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05

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
K/A	0.546	ambiguous	0.5121	ambiguous	-0.202	Destabilizing	0.4	N	0.341	neutral	None	None	None	None	I
K/C	0.8062	likely_pathogenic	0.7949	pathogenic	-0.349	Destabilizing	0.992	D	0.255	neutral	None	None	None	None	I
K/D	0.7473	likely_pathogenic	0.7256	pathogenic	0.254	Stabilizing	0.447	N	0.337	neutral	None	None	None	None	I
K/E	0.2212	likely_benign	0.205	benign	0.315	Stabilizing	0.016	N	0.139	neutral	N	0.506526304	None	None	I
K/F	0.8977	likely_pathogenic	0.8845	pathogenic	-0.084	Destabilizing	0.972	D	0.27	neutral	None	None	None	None	I
K/G	0.5745	likely_pathogenic	0.5378	ambiguous	-0.497	Destabilizing	0.617	D	0.344	neutral	None	None	None	None	I
K/H	0.3512	ambiguous	0.3352	benign	-0.742	Destabilizing	0.92	D	0.309	neutral	None	None	None	None	I
K/I	0.6534	likely_pathogenic	0.6216	pathogenic	0.521	Stabilizing	0.85	D	0.293	neutral	None	None	None	None	I
K/L	0.5562	ambiguous	0.5341	ambiguous	0.521	Stabilizing	0.617	D	0.351	neutral	None	None	None	None	I
K/M	0.4157	ambiguous	0.4172	ambiguous	0.279	Stabilizing	0.963	D	0.313	neutral	N	0.503787493	None	None	I
K/N	0.5658	likely_pathogenic	0.55	ambiguous	None	Stabilizing	0.549	D	0.247	neutral	N	0.502773534	None	None	I
K/P	0.949	likely_pathogenic	0.9363	pathogenic	0.31	Stabilizing	0.92	D	0.337	neutral	None	None	None	None	I
K/Q	0.12	likely_benign	0.1165	benign	-0.123	Destabilizing	0.016	N	0.166	neutral	N	0.473931096	None	None	I
K/R	0.0844	likely_benign	0.0819	benign	-0.231	Destabilizing	0.004	N	0.221	neutral	N	0.501235127	None	None	I
K/S	0.5295	ambiguous	0.4986	ambiguous	-0.624	Destabilizing	0.25	N	0.279	neutral	None	None	None	None	I
K/T	0.2845	likely_benign	0.2737	benign	-0.38	Destabilizing	0.007	N	0.149	neutral	D	0.523610555	None	None	I
K/V	0.5731	likely_pathogenic	0.5414	ambiguous	0.31	Stabilizing	0.617	D	0.33	neutral	None	None	None	None	I
K/W	0.8458	likely_pathogenic	0.8098	pathogenic	0.003	Stabilizing	0.992	D	0.296	neutral	None	None	None	None	I
K/Y	0.7789	likely_pathogenic	0.755	pathogenic	0.309	Stabilizing	0.972	D	0.275	neutral	None	None	None	None	I

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.