TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17802	53629;53630;53631	chr2:178607198;178607197;178607196	chr2:179471925;179471924;179471923
N2AB	16161	48706;48707;48708	chr2:178607198;178607197;178607196	chr2:179471925;179471924;179471923
N2A	15234	45925;45926;45927	chr2:178607198;178607197;178607196	chr2:179471925;179471924;179471923
N2B	8737	26434;26435;26436	chr2:178607198;178607197;178607196	chr2:179471925;179471924;179471923
Novex-1	8862	26809;26810;26811	chr2:178607198;178607197;178607196	chr2:179471925;179471924;179471923
Novex-2	8929	27010;27011;27012	chr2:178607198;178607197;178607196	chr2:179471925;179471924;179471923
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-17
• Domain position: 39
• Structural Position: 41
• Q(SASA): 0.1706
• 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
E/D	None	None	0.998	N	0.605	0.291	0.251116650651	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	None	0	0	0	0	0
E/G	None	None	0.999	D	0.746	0.405	0.563062970572	gnomAD-4.0.0	1.59287E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86151E-06	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
E/A	0.9373	likely_pathogenic	0.925	pathogenic	-1.653	Destabilizing	0.994	D	0.604	neutral	D	0.528278897	None	None	N
E/C	0.99	likely_pathogenic	0.9892	pathogenic	-0.841	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
E/D	0.9313	likely_pathogenic	0.9267	pathogenic	-1.895	Destabilizing	0.998	D	0.605	neutral	N	0.489032194	None	None	N
E/F	0.9952	likely_pathogenic	0.9926	pathogenic	-1.334	Destabilizing	0.998	D	0.822	deleterious	None	None	None	None	N
E/G	0.9642	likely_pathogenic	0.9572	pathogenic	-2.029	Highly Destabilizing	0.999	D	0.746	deleterious	D	0.530053324	None	None	N
E/H	0.9882	likely_pathogenic	0.985	pathogenic	-1.194	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
E/I	0.9791	likely_pathogenic	0.9685	pathogenic	-0.566	Destabilizing	0.995	D	0.783	deleterious	None	None	None	None	N
E/K	0.9711	likely_pathogenic	0.9609	pathogenic	-1.671	Destabilizing	0.998	D	0.657	neutral	N	0.508907194	None	None	N
E/L	0.9716	likely_pathogenic	0.9587	pathogenic	-0.566	Destabilizing	0.269	N	0.622	neutral	None	None	None	None	N
E/M	0.9745	likely_pathogenic	0.9633	pathogenic	0.146	Stabilizing	0.999	D	0.814	deleterious	None	None	None	None	N
E/N	0.9902	likely_pathogenic	0.9884	pathogenic	-1.883	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
E/P	0.9997	likely_pathogenic	0.9996	pathogenic	-0.916	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
E/Q	0.7264	likely_pathogenic	0.6951	pathogenic	-1.581	Destabilizing	0.999	D	0.743	deleterious	N	0.507917878	None	None	N
E/R	0.9767	likely_pathogenic	0.9712	pathogenic	-1.49	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
E/S	0.9583	likely_pathogenic	0.9484	pathogenic	-2.488	Highly Destabilizing	0.999	D	0.68	prob.neutral	None	None	None	None	N
E/T	0.9787	likely_pathogenic	0.9686	pathogenic	-2.127	Highly Destabilizing	0.999	D	0.733	prob.delet.	None	None	None	None	N
E/V	0.9573	likely_pathogenic	0.9355	pathogenic	-0.916	Destabilizing	0.978	D	0.686	prob.neutral	N	0.51093511	None	None	N
E/W	0.9978	likely_pathogenic	0.9968	pathogenic	-1.445	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	N
E/Y	0.9932	likely_pathogenic	0.9897	pathogenic	-1.173	Destabilizing	1.0	D	0.811	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.