TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5614	17065;17066;17067	chr2:178732129;178732128;178732127	chr2:179596856;179596855;179596854
N2AB	5297	16114;16115;16116	chr2:178732129;178732128;178732127	chr2:179596856;179596855;179596854
N2A	4370	13333;13334;13335	chr2:178732129;178732128;178732127	chr2:179596856;179596855;179596854
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: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Ig-39
• Domain position: 72
• Structural Position: 154
• Q(SASA): 0.2374
• 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	rs2080651364	None	0.999	D	0.824	0.743	0.885400995387	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
Y/C	rs2080651364	None	0.999	D	0.824	0.743	0.885400995387	gnomAD-4.0.0	6.57073E-06	None	None	None	None	N	None	2.4122E-05	0	None	0	0	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	0.9558	likely_pathogenic	0.9715	pathogenic	-2.826	Highly Destabilizing	0.944	D	0.799	deleterious	None	None	None	None	N
Y/C	0.6557	likely_pathogenic	0.7485	pathogenic	-2.295	Highly Destabilizing	0.999	D	0.824	deleterious	D	0.661316994	None	None	N
Y/D	0.9789	likely_pathogenic	0.9872	pathogenic	-2.852	Highly Destabilizing	0.996	D	0.873	deleterious	D	0.661316994	None	None	N
Y/E	0.9884	likely_pathogenic	0.9925	pathogenic	-2.635	Highly Destabilizing	0.997	D	0.848	deleterious	None	None	None	None	N
Y/F	0.1109	likely_benign	0.1175	benign	-1.113	Destabilizing	0.039	N	0.471	neutral	D	0.552301407	None	None	N
Y/G	0.9561	likely_pathogenic	0.971	pathogenic	-3.276	Highly Destabilizing	0.992	D	0.869	deleterious	None	None	None	None	N
Y/H	0.8423	likely_pathogenic	0.8854	pathogenic	-2.04	Highly Destabilizing	0.996	D	0.751	deleterious	D	0.66111519	None	None	N
Y/I	0.5457	ambiguous	0.5824	pathogenic	-1.348	Destabilizing	0.968	D	0.79	deleterious	None	None	None	None	N
Y/K	0.9791	likely_pathogenic	0.9855	pathogenic	-2.196	Highly Destabilizing	0.992	D	0.85	deleterious	None	None	None	None	N
Y/L	0.5967	likely_pathogenic	0.6336	pathogenic	-1.348	Destabilizing	0.895	D	0.744	deleterious	None	None	None	None	N
Y/M	0.7891	likely_pathogenic	0.8305	pathogenic	-1.385	Destabilizing	0.998	D	0.781	deleterious	None	None	None	None	N
Y/N	0.8849	likely_pathogenic	0.9183	pathogenic	-2.985	Highly Destabilizing	0.996	D	0.843	deleterious	D	0.661316994	None	None	N
Y/P	0.9955	likely_pathogenic	0.9971	pathogenic	-1.854	Destabilizing	0.997	D	0.874	deleterious	None	None	None	None	N
Y/Q	0.9767	likely_pathogenic	0.9845	pathogenic	-2.663	Highly Destabilizing	0.997	D	0.783	deleterious	None	None	None	None	N
Y/R	0.9584	likely_pathogenic	0.9698	pathogenic	-2.079	Highly Destabilizing	0.992	D	0.836	deleterious	None	None	None	None	N
Y/S	0.943	likely_pathogenic	0.9627	pathogenic	-3.481	Highly Destabilizing	0.989	D	0.842	deleterious	D	0.661316994	None	None	N
Y/T	0.9516	likely_pathogenic	0.9669	pathogenic	-3.125	Highly Destabilizing	0.992	D	0.843	deleterious	None	None	None	None	N
Y/V	0.5332	ambiguous	0.5697	pathogenic	-1.854	Destabilizing	0.895	D	0.767	deleterious	None	None	None	None	N
Y/W	0.6822	likely_pathogenic	0.7353	pathogenic	-0.458	Destabilizing	0.999	D	0.731	prob.delet.	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.