TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31945	96058;96059;96060	chr2:178544396;178544395;178544394	chr2:179409123;179409122;179409121
N2AB	30304	91135;91136;91137	chr2:178544396;178544395;178544394	chr2:179409123;179409122;179409121
N2A	29377	88354;88355;88356	chr2:178544396;178544395;178544394	chr2:179409123;179409122;179409121
N2B	22880	68863;68864;68865	chr2:178544396;178544395;178544394	chr2:179409123;179409122;179409121
Novex-1	23005	69238;69239;69240	chr2:178544396;178544395;178544394	chr2:179409123;179409122;179409121
Novex-2	23072	69439;69440;69441	chr2:178544396;178544395;178544394	chr2:179409123;179409122;179409121
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-121
• Domain position: 37
• Structural Position: 39
• Q(SASA): 0.1614
• 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	None	None	0.37	N	0.294	0.166	0.383256108077	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-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
V/A	0.4501	ambiguous	0.4671	ambiguous	-2.469	Highly Destabilizing	0.978	D	0.643	neutral	N	0.470595089	None	None	N
V/C	0.722	likely_pathogenic	0.7255	pathogenic	-1.879	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
V/D	0.7966	likely_pathogenic	0.8102	pathogenic	-3.571	Highly Destabilizing	0.999	D	0.819	deleterious	N	0.471493689	None	None	N
V/E	0.594	likely_pathogenic	0.6334	pathogenic	-3.328	Highly Destabilizing	0.999	D	0.793	deleterious	None	None	None	None	N
V/F	0.2345	likely_benign	0.2579	benign	-1.584	Destabilizing	0.997	D	0.785	deleterious	N	0.515825286	None	None	N
V/G	0.6507	likely_pathogenic	0.6314	pathogenic	-2.979	Highly Destabilizing	0.999	D	0.804	deleterious	N	0.489966792	None	None	N
V/H	0.7096	likely_pathogenic	0.7352	pathogenic	-2.838	Highly Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
V/I	0.0686	likely_benign	0.0706	benign	-1.005	Destabilizing	0.37	N	0.294	neutral	N	0.473901305	None	None	N
V/K	0.6477	likely_pathogenic	0.6711	pathogenic	-2.341	Highly Destabilizing	0.999	D	0.796	deleterious	None	None	None	None	N
V/L	0.2026	likely_benign	0.2149	benign	-1.005	Destabilizing	0.9	D	0.569	neutral	N	0.479133767	None	None	N
V/M	0.1871	likely_benign	0.2077	benign	-0.958	Destabilizing	0.998	D	0.75	deleterious	None	None	None	None	N
V/N	0.6048	likely_pathogenic	0.6334	pathogenic	-2.799	Highly Destabilizing	0.999	D	0.813	deleterious	None	None	None	None	N
V/P	0.9869	likely_pathogenic	0.9834	pathogenic	-1.474	Destabilizing	0.999	D	0.815	deleterious	None	None	None	None	N
V/Q	0.5581	ambiguous	0.5856	pathogenic	-2.608	Highly Destabilizing	0.999	D	0.791	deleterious	None	None	None	None	N
V/R	0.5753	likely_pathogenic	0.5916	pathogenic	-2.069	Highly Destabilizing	0.999	D	0.809	deleterious	None	None	None	None	N
V/S	0.4973	ambiguous	0.5173	ambiguous	-3.275	Highly Destabilizing	0.999	D	0.797	deleterious	None	None	None	None	N
V/T	0.3516	ambiguous	0.3842	ambiguous	-2.913	Highly Destabilizing	0.992	D	0.71	prob.delet.	None	None	None	None	N
V/W	0.8676	likely_pathogenic	0.8711	pathogenic	-2.242	Highly Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
V/Y	0.6084	likely_pathogenic	0.6269	pathogenic	-1.891	Destabilizing	0.999	D	0.799	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.