TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8761	26506;26507;26508	chr2:178714493;178714492;178714491	chr2:179579220;179579219;179579218
N2AB	8444	25555;25556;25557	chr2:178714493;178714492;178714491	chr2:179579220;179579219;179579218
N2A	7517	22774;22775;22776	chr2:178714493;178714492;178714491	chr2:179579220;179579219;179579218
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: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Ig-73
• Domain position: 26
• Structural Position: 40
• Q(SASA): 0.3471
• 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
G/S	rs369385294	-0.776	1.0	D	0.842	0.667	None	gnomAD-2.1.1	5.37E-05	None	None	None	None	N	None	4.14E-05	0	None	0	0	None	0	None	0	1.09714E-04	0
G/S	rs369385294	-0.776	1.0	D	0.842	0.667	None	gnomAD-3.1.2	5.26E-05	None	None	None	None	N	None	7.24E-05	0	0	0	0	None	0	0	7.35E-05	0	0
G/S	rs369385294	-0.776	1.0	D	0.842	0.667	None	gnomAD-4.0.0	1.41941E-04	None	None	None	None	N	None	8.01325E-05	0	None	0	0	None	0	0	1.86499E-04	0	4.80446E-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
G/A	0.3277	likely_benign	0.5219	ambiguous	-0.425	Destabilizing	0.999	D	0.773	deleterious	D	0.57484102	None	None	N
G/C	0.7658	likely_pathogenic	0.927	pathogenic	-0.748	Destabilizing	1.0	D	0.718	prob.delet.	D	0.62213117	None	None	N
G/D	0.7425	likely_pathogenic	0.9116	pathogenic	-1.165	Destabilizing	1.0	D	0.854	deleterious	D	0.601186349	None	None	N
G/E	0.8249	likely_pathogenic	0.953	pathogenic	-1.307	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
G/F	0.9467	likely_pathogenic	0.9831	pathogenic	-1.049	Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	N
G/H	0.949	likely_pathogenic	0.9869	pathogenic	-0.923	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
G/I	0.8455	likely_pathogenic	0.9575	pathogenic	-0.412	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
G/K	0.9505	likely_pathogenic	0.988	pathogenic	-1.25	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
G/L	0.8893	likely_pathogenic	0.9664	pathogenic	-0.412	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
G/M	0.9069	likely_pathogenic	0.975	pathogenic	-0.383	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
G/N	0.8335	likely_pathogenic	0.9467	pathogenic	-0.726	Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
G/P	0.9819	likely_pathogenic	0.9945	pathogenic	-0.38	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
G/Q	0.9297	likely_pathogenic	0.9818	pathogenic	-1.023	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
G/R	0.9208	likely_pathogenic	0.9788	pathogenic	-0.762	Destabilizing	1.0	D	0.814	deleterious	D	0.647265673	None	None	N
G/S	0.3171	likely_benign	0.5774	pathogenic	-0.796	Destabilizing	1.0	D	0.842	deleterious	D	0.588851262	None	None	N
G/T	0.6427	likely_pathogenic	0.8532	pathogenic	-0.886	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
G/V	0.7173	likely_pathogenic	0.9023	pathogenic	-0.38	Destabilizing	1.0	D	0.801	deleterious	D	0.647265673	None	None	N
G/W	0.8997	likely_pathogenic	0.9687	pathogenic	-1.288	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
G/Y	0.9043	likely_pathogenic	0.9731	pathogenic	-0.943	Destabilizing	1.0	D	0.757	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.