TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20687	62284;62285;62286	chr2:178589666;178589665;178589664	chr2:179454393;179454392;179454391
N2AB	19046	57361;57362;57363	chr2:178589666;178589665;178589664	chr2:179454393;179454392;179454391
N2A	18119	54580;54581;54582	chr2:178589666;178589665;178589664	chr2:179454393;179454392;179454391
N2B	11622	35089;35090;35091	chr2:178589666;178589665;178589664	chr2:179454393;179454392;179454391
Novex-1	11747	35464;35465;35466	chr2:178589666;178589665;178589664	chr2:179454393;179454392;179454391
Novex-2	11814	35665;35666;35667	chr2:178589666;178589665;178589664	chr2:179454393;179454392;179454391
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Fn3-38
• Domain position: 20
• Structural Position: 22
• Q(SASA): 0.0854
• 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
L/V	rs76587526	-2.034	0.999	D	0.564	0.285	None	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	2.68E-05	0
L/V	rs76587526	-2.034	0.999	D	0.564	0.285	None	gnomAD-4.0.0	2.25825E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.7887E-05	0	3.31356E-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
L/A	0.9909	likely_pathogenic	0.9875	pathogenic	-2.82	Highly Destabilizing	0.999	D	0.714	prob.delet.	None	None	None	None	N
L/C	0.9703	likely_pathogenic	0.9655	pathogenic	-1.719	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
L/D	0.9999	likely_pathogenic	0.9999	pathogenic	-3.034	Highly Destabilizing	1.0	D	0.927	deleterious	None	None	None	None	N
L/E	0.9994	likely_pathogenic	0.9991	pathogenic	-2.781	Highly Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
L/F	0.8866	likely_pathogenic	0.8712	pathogenic	-1.616	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
L/G	0.9984	likely_pathogenic	0.9977	pathogenic	-3.272	Highly Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
L/H	0.9987	likely_pathogenic	0.9981	pathogenic	-2.756	Highly Destabilizing	1.0	D	0.9	deleterious	None	None	None	None	N
L/I	0.3113	likely_benign	0.3034	benign	-1.423	Destabilizing	0.999	D	0.548	neutral	N	0.49893861	None	None	N
L/K	0.9986	likely_pathogenic	0.9976	pathogenic	-2.234	Highly Destabilizing	1.0	D	0.892	deleterious	None	None	None	None	N
L/M	0.5797	likely_pathogenic	0.56	ambiguous	-1.597	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
L/N	0.9996	likely_pathogenic	0.9993	pathogenic	-2.889	Highly Destabilizing	1.0	D	0.929	deleterious	None	None	None	None	N
L/P	0.9994	likely_pathogenic	0.9991	pathogenic	-1.888	Destabilizing	1.0	D	0.931	deleterious	D	0.533293597	None	None	N
L/Q	0.9975	likely_pathogenic	0.9963	pathogenic	-2.552	Highly Destabilizing	1.0	D	0.929	deleterious	D	0.533293597	None	None	N
L/R	0.9968	likely_pathogenic	0.9956	pathogenic	-2.312	Highly Destabilizing	1.0	D	0.913	deleterious	D	0.533293597	None	None	N
L/S	0.9993	likely_pathogenic	0.999	pathogenic	-3.197	Highly Destabilizing	1.0	D	0.892	deleterious	None	None	None	None	N
L/T	0.9943	likely_pathogenic	0.9922	pathogenic	-2.82	Highly Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
L/V	0.4072	ambiguous	0.396	ambiguous	-1.888	Destabilizing	0.999	D	0.564	neutral	D	0.522831403	None	None	N
L/W	0.995	likely_pathogenic	0.9942	pathogenic	-1.672	Destabilizing	1.0	D	0.876	deleterious	None	None	None	None	N
L/Y	0.9957	likely_pathogenic	0.9947	pathogenic	-1.783	Destabilizing	1.0	D	0.841	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.