TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8475	25648;25649;25650	chr2:178717311;178717310;178717309	chr2:179582038;179582037;179582036
N2AB	8158	24697;24698;24699	chr2:178717311;178717310;178717309	chr2:179582038;179582037;179582036
N2A	7231	21916;21917;21918	chr2:178717311;178717310;178717309	chr2:179582038;179582037;179582036
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: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Ig-70
• Domain position: 20
• Structural Position: 30
• Q(SASA): 0.0982
• 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
F/I	rs772111560	None	0.088	N	0.561	0.401	0.286081765059	gnomAD-4.0.0	1.1633E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.34937E-05	0	3.31367E-05

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
F/A	0.9908	likely_pathogenic	0.9891	pathogenic	-2.254	Highly Destabilizing	0.236	N	0.685	prob.neutral	None	None	None	None	N
F/C	0.9663	likely_pathogenic	0.9621	pathogenic	-1.48	Destabilizing	0.989	D	0.848	deleterious	D	0.608235241	None	None	N
F/D	0.9996	likely_pathogenic	0.9995	pathogenic	-2.701	Highly Destabilizing	0.994	D	0.816	deleterious	None	None	None	None	N
F/E	0.9993	likely_pathogenic	0.9991	pathogenic	-2.443	Highly Destabilizing	0.933	D	0.801	deleterious	None	None	None	None	N
F/G	0.9966	likely_pathogenic	0.9956	pathogenic	-2.744	Highly Destabilizing	0.979	D	0.753	deleterious	None	None	None	None	N
F/H	0.9943	likely_pathogenic	0.9925	pathogenic	-1.75	Destabilizing	0.907	D	0.767	deleterious	None	None	None	None	N
F/I	0.7258	likely_pathogenic	0.7228	pathogenic	-0.653	Destabilizing	0.088	N	0.561	neutral	N	0.511135195	None	None	N
F/K	0.9992	likely_pathogenic	0.999	pathogenic	-1.683	Destabilizing	0.95	D	0.782	deleterious	None	None	None	None	N
F/L	0.9092	likely_pathogenic	0.906	pathogenic	-0.653	Destabilizing	None	N	0.257	neutral	N	0.403956509	None	None	N
F/M	0.8506	likely_pathogenic	0.8407	pathogenic	-0.619	Destabilizing	0.092	N	0.639	neutral	None	None	None	None	N
F/N	0.9983	likely_pathogenic	0.9977	pathogenic	-2.286	Highly Destabilizing	0.994	D	0.815	deleterious	None	None	None	None	N
F/P	0.9999	likely_pathogenic	0.9998	pathogenic	-1.199	Destabilizing	0.999	D	0.855	deleterious	None	None	None	None	N
F/Q	0.9979	likely_pathogenic	0.9974	pathogenic	-2.049	Highly Destabilizing	0.99	D	0.855	deleterious	None	None	None	None	N
F/R	0.9969	likely_pathogenic	0.9962	pathogenic	-1.646	Destabilizing	0.993	D	0.839	deleterious	None	None	None	None	N
F/S	0.9945	likely_pathogenic	0.9926	pathogenic	-2.879	Highly Destabilizing	0.576	D	0.571	neutral	D	0.608235241	None	None	N
F/T	0.9955	likely_pathogenic	0.9943	pathogenic	-2.489	Highly Destabilizing	0.979	D	0.729	prob.delet.	None	None	None	None	N
F/V	0.7585	likely_pathogenic	0.7594	pathogenic	-1.199	Destabilizing	0.066	N	0.647	neutral	N	0.500813249	None	None	N
F/W	0.9248	likely_pathogenic	0.9032	pathogenic	0.097	Stabilizing	0.986	D	0.62	neutral	None	None	None	None	N
F/Y	0.6811	likely_pathogenic	0.6402	pathogenic	-0.308	Destabilizing	0.298	N	0.587	neutral	D	0.582495325	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.