TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21141	63646;63647;63648	chr2:178587986;178587985;178587984	chr2:179452713;179452712;179452711
N2AB	19500	58723;58724;58725	chr2:178587986;178587985;178587984	chr2:179452713;179452712;179452711
N2A	18573	55942;55943;55944	chr2:178587986;178587985;178587984	chr2:179452713;179452712;179452711
N2B	12076	36451;36452;36453	chr2:178587986;178587985;178587984	chr2:179452713;179452712;179452711
Novex-1	12201	36826;36827;36828	chr2:178587986;178587985;178587984	chr2:179452713;179452712;179452711
Novex-2	12268	37027;37028;37029	chr2:178587986;178587985;178587984	chr2:179452713;179452712;179452711
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-41
• Domain position: 78
• Structural Position: 104
• Q(SASA): 0.0969
• 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
Y/C	rs762123565	-2.189	1.0	D	0.791	0.875	0.931094108997	gnomAD-2.1.1	8.1E-06	None	None	None	None	N	None	0	0	None	0	1.13276E-04	None	0	None	0	0	0
Y/C	rs762123565	-2.189	1.0	D	0.791	0.875	0.931094108997	gnomAD-4.0.0	3.18897E-06	None	None	None	None	N	None	0	0	None	0	5.58878E-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
Y/A	0.9864	likely_pathogenic	0.9872	pathogenic	-3.258	Highly Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
Y/C	0.8851	likely_pathogenic	0.8911	pathogenic	-1.918	Destabilizing	1.0	D	0.791	deleterious	D	0.676418364	None	None	N
Y/D	0.9871	likely_pathogenic	0.9872	pathogenic	-3.908	Highly Destabilizing	1.0	D	0.839	deleterious	D	0.676418364	None	None	N
Y/E	0.9953	likely_pathogenic	0.9956	pathogenic	-3.706	Highly Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
Y/F	0.2767	likely_benign	0.2895	benign	-1.314	Destabilizing	0.999	D	0.764	deleterious	D	0.61493581	None	None	N
Y/G	0.9705	likely_pathogenic	0.9694	pathogenic	-3.646	Highly Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
Y/H	0.9331	likely_pathogenic	0.9392	pathogenic	-2.355	Highly Destabilizing	1.0	D	0.795	deleterious	D	0.660166839	None	None	N
Y/I	0.9417	likely_pathogenic	0.9443	pathogenic	-1.947	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
Y/K	0.9923	likely_pathogenic	0.993	pathogenic	-2.565	Highly Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
Y/L	0.912	likely_pathogenic	0.9178	pathogenic	-1.947	Destabilizing	0.999	D	0.798	deleterious	None	None	None	None	N
Y/M	0.9495	likely_pathogenic	0.9522	pathogenic	-1.626	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
Y/N	0.9225	likely_pathogenic	0.9226	pathogenic	-3.401	Highly Destabilizing	1.0	D	0.839	deleterious	D	0.67621656	None	None	N
Y/P	0.9979	likely_pathogenic	0.998	pathogenic	-2.402	Highly Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
Y/Q	0.9921	likely_pathogenic	0.9931	pathogenic	-3.151	Highly Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
Y/R	0.9811	likely_pathogenic	0.9829	pathogenic	-2.305	Highly Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
Y/S	0.9701	likely_pathogenic	0.9713	pathogenic	-3.65	Highly Destabilizing	1.0	D	0.848	deleterious	D	0.676418364	None	None	N
Y/T	0.9819	likely_pathogenic	0.9832	pathogenic	-3.338	Highly Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
Y/V	0.8958	likely_pathogenic	0.9004	pathogenic	-2.402	Highly Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
Y/W	0.7178	likely_pathogenic	0.7381	pathogenic	-0.682	Destabilizing	1.0	D	0.785	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.