TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19474	58645;58646;58647	chr2:178593973;178593972;178593971	chr2:179458700;179458699;179458698
N2AB	17833	53722;53723;53724	chr2:178593973;178593972;178593971	chr2:179458700;179458699;179458698
N2A	16906	50941;50942;50943	chr2:178593973;178593972;178593971	chr2:179458700;179458699;179458698
N2B	10409	31450;31451;31452	chr2:178593973;178593972;178593971	chr2:179458700;179458699;179458698
Novex-1	10534	31825;31826;31827	chr2:178593973;178593972;178593971	chr2:179458700;179458699;179458698
Novex-2	10601	32026;32027;32028	chr2:178593973;178593972;178593971	chr2:179458700;179458699;179458698
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: Ig-118
• Domain position: 84
• Structural Position: 174
• Q(SASA): 0.1631
• 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	rs1307485937	None	0.543	N	0.273	0.179	0.388653054685	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
V/I	rs1307485937	None	0.543	N	0.273	0.179	0.388653054685	gnomAD-4.0.0	6.57445E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47033E-05	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	0.8809	likely_pathogenic	0.8596	pathogenic	-2.41	Highly Destabilizing	0.994	D	0.604	neutral	N	0.500074741	None	None	N
V/C	0.9606	likely_pathogenic	0.958	pathogenic	-2.512	Highly Destabilizing	1.0	D	0.782	deleterious	None	None	None	None	N
V/D	0.9962	likely_pathogenic	0.9945	pathogenic	-2.966	Highly Destabilizing	0.999	D	0.841	deleterious	N	0.511938025	None	None	N
V/E	0.989	likely_pathogenic	0.9846	pathogenic	-2.716	Highly Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
V/F	0.7646	likely_pathogenic	0.7149	pathogenic	-1.528	Destabilizing	0.998	D	0.804	deleterious	N	0.499314272	None	None	N
V/G	0.9023	likely_pathogenic	0.8771	pathogenic	-2.991	Highly Destabilizing	0.999	D	0.827	deleterious	N	0.511938025	None	None	N
V/H	0.9971	likely_pathogenic	0.9959	pathogenic	-2.67	Highly Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
V/I	0.0921	likely_benign	0.092	benign	-0.764	Destabilizing	0.543	D	0.273	neutral	N	0.500290112	None	None	N
V/K	0.9929	likely_pathogenic	0.9895	pathogenic	-2.033	Highly Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
V/L	0.4708	ambiguous	0.458	ambiguous	-0.764	Destabilizing	0.948	D	0.587	neutral	N	0.485610582	None	None	N
V/M	0.6386	likely_pathogenic	0.6084	pathogenic	-1.112	Destabilizing	0.999	D	0.74	deleterious	None	None	None	None	N
V/N	0.9878	likely_pathogenic	0.9837	pathogenic	-2.487	Highly Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
V/P	0.9925	likely_pathogenic	0.9912	pathogenic	-1.288	Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	N
V/Q	0.9902	likely_pathogenic	0.9873	pathogenic	-2.281	Highly Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
V/R	0.988	likely_pathogenic	0.9828	pathogenic	-1.896	Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	N
V/S	0.9775	likely_pathogenic	0.9722	pathogenic	-3.2	Highly Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
V/T	0.9384	likely_pathogenic	0.9283	pathogenic	-2.782	Highly Destabilizing	0.996	D	0.692	prob.neutral	None	None	None	None	N
V/W	0.9949	likely_pathogenic	0.9925	pathogenic	-1.961	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
V/Y	0.9804	likely_pathogenic	0.9724	pathogenic	-1.643	Destabilizing	1.0	D	0.787	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.