TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6128	18607;18608;18609	chr2:178729871;178729870;178729869	chr2:179594598;179594597;179594596
N2AB	5811	17656;17657;17658	chr2:178729871;178729870;178729869	chr2:179594598;179594597;179594596
N2A	4884	14875;14876;14877	chr2:178729871;178729870;178729869	chr2:179594598;179594597;179594596
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: Q
• RefSeq wild type transcript codon: CAA
• RefSeq wild type template codon: GTT
• Domain: Ig-45
• Domain position: 24
• Structural Position: 34
• Q(SASA): 0.3392
• 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
Q/R	None	None	0.012	N	0.327	0.258	0.143124449307	gnomAD-4.0.0	1.59179E-06	None	None	None	None	N	None	0	0	None	0	2.77793E-05	None	0	0	0	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
Q/A	0.2829	likely_benign	0.2638	benign	-0.827	Destabilizing	0.842	D	0.492	neutral	None	None	None	None	N
Q/C	0.6494	likely_pathogenic	0.6197	pathogenic	-0.135	Destabilizing	0.998	D	0.677	prob.neutral	None	None	None	None	N
Q/D	0.445	ambiguous	0.3985	ambiguous	-0.767	Destabilizing	0.842	D	0.452	neutral	None	None	None	None	N
Q/E	0.0808	likely_benign	0.0798	benign	-0.602	Destabilizing	0.625	D	0.405	neutral	N	0.478184909	None	None	N
Q/F	0.6631	likely_pathogenic	0.6198	pathogenic	-0.329	Destabilizing	0.974	D	0.683	prob.neutral	None	None	None	None	N
Q/G	0.3565	ambiguous	0.3328	benign	-1.24	Destabilizing	0.842	D	0.577	neutral	None	None	None	None	N
Q/H	0.1918	likely_benign	0.1825	benign	-0.912	Destabilizing	0.028	N	0.3	neutral	N	0.516724655	None	None	N
Q/I	0.3742	ambiguous	0.345	ambiguous	0.262	Stabilizing	0.974	D	0.679	prob.neutral	None	None	None	None	N
Q/K	0.0965	likely_benign	0.0981	benign	-0.355	Destabilizing	0.454	N	0.452	neutral	N	0.406458097	None	None	N
Q/L	0.1561	likely_benign	0.1419	benign	0.262	Stabilizing	0.801	D	0.589	neutral	N	0.512492271	None	None	N
Q/M	0.3926	ambiguous	0.3655	ambiguous	0.671	Stabilizing	0.991	D	0.534	neutral	None	None	None	None	N
Q/N	0.3474	ambiguous	0.2998	benign	-1.031	Destabilizing	0.842	D	0.451	neutral	None	None	None	None	N
Q/P	0.2931	likely_benign	0.3032	benign	-0.07	Destabilizing	0.989	D	0.623	neutral	D	0.537003926	None	None	N
Q/R	0.0942	likely_benign	0.0941	benign	-0.367	Destabilizing	0.012	N	0.327	neutral	N	0.445112486	None	None	N
Q/S	0.3282	likely_benign	0.2883	benign	-1.229	Destabilizing	0.842	D	0.437	neutral	None	None	None	None	N
Q/T	0.2382	likely_benign	0.2125	benign	-0.855	Destabilizing	0.915	D	0.554	neutral	None	None	None	None	N
Q/V	0.2727	likely_benign	0.248	benign	-0.07	Destabilizing	0.974	D	0.615	neutral	None	None	None	None	N
Q/W	0.4626	ambiguous	0.4333	ambiguous	-0.194	Destabilizing	0.998	D	0.659	neutral	None	None	None	None	N
Q/Y	0.4293	ambiguous	0.3884	ambiguous	0.055	Stabilizing	0.949	D	0.624	neutral	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.