TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20901	62926;62927;62928	chr2:178589024;178589023;178589022	chr2:179453751;179453750;179453749
N2AB	19260	58003;58004;58005	chr2:178589024;178589023;178589022	chr2:179453751;179453750;179453749
N2A	18333	55222;55223;55224	chr2:178589024;178589023;178589022	chr2:179453751;179453750;179453749
N2B	11836	35731;35732;35733	chr2:178589024;178589023;178589022	chr2:179453751;179453750;179453749
Novex-1	11961	36106;36107;36108	chr2:178589024;178589023;178589022	chr2:179453751;179453750;179453749
Novex-2	12028	36307;36308;36309	chr2:178589024;178589023;178589022	chr2:179453751;179453750;179453749
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: Fn3-39
• Domain position: 38
• Structural Position: 40
• Q(SASA): 0.0911
• 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/I	None	None	0.058	N	0.364	0.08	0.187945064343	gnomAD-4.0.0	1.37149E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79947E-06	0	0
L/P	None	None	0.99	N	0.855	0.575	0.854063423762	gnomAD-4.0.0	1.59902E-06	None	None	None	None	N	None	0	0	None	0	2.79298E-05	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
L/A	0.8726	likely_pathogenic	0.8764	pathogenic	-2.694	Highly Destabilizing	0.754	D	0.605	neutral	None	None	None	None	N
L/C	0.8676	likely_pathogenic	0.8784	pathogenic	-2.013	Highly Destabilizing	0.998	D	0.694	prob.neutral	None	None	None	None	N
L/D	0.9995	likely_pathogenic	0.9995	pathogenic	-3.277	Highly Destabilizing	0.993	D	0.854	deleterious	None	None	None	None	N
L/E	0.9956	likely_pathogenic	0.9953	pathogenic	-2.944	Highly Destabilizing	0.978	D	0.851	deleterious	None	None	None	None	N
L/F	0.6445	likely_pathogenic	0.6554	pathogenic	-1.596	Destabilizing	0.956	D	0.656	neutral	None	None	None	None	N
L/G	0.9914	likely_pathogenic	0.9923	pathogenic	-3.336	Highly Destabilizing	0.978	D	0.847	deleterious	None	None	None	None	N
L/H	0.9906	likely_pathogenic	0.9905	pathogenic	-3.027	Highly Destabilizing	0.998	D	0.796	deleterious	None	None	None	None	N
L/I	0.0919	likely_benign	0.0838	benign	-0.772	Destabilizing	0.058	N	0.364	neutral	N	0.384276592	None	None	N
L/K	0.9942	likely_pathogenic	0.9937	pathogenic	-2.08	Highly Destabilizing	0.978	D	0.83	deleterious	None	None	None	None	N
L/M	0.2799	likely_benign	0.2922	benign	-0.957	Destabilizing	0.956	D	0.621	neutral	None	None	None	None	N
L/N	0.9969	likely_pathogenic	0.9969	pathogenic	-2.78	Highly Destabilizing	0.993	D	0.849	deleterious	None	None	None	None	N
L/P	0.9945	likely_pathogenic	0.9947	pathogenic	-1.402	Destabilizing	0.99	D	0.855	deleterious	N	0.488986649	None	None	N
L/Q	0.9847	likely_pathogenic	0.9843	pathogenic	-2.412	Highly Destabilizing	0.99	D	0.838	deleterious	N	0.500342955	None	None	N
L/R	0.9881	likely_pathogenic	0.9877	pathogenic	-2.153	Highly Destabilizing	0.971	D	0.841	deleterious	N	0.500342955	None	None	N
L/S	0.9871	likely_pathogenic	0.9881	pathogenic	-3.414	Highly Destabilizing	0.956	D	0.825	deleterious	None	None	None	None	N
L/T	0.8872	likely_pathogenic	0.8853	pathogenic	-2.902	Highly Destabilizing	0.956	D	0.68	prob.neutral	None	None	None	None	N
L/V	0.0896	likely_benign	0.0825	benign	-1.402	Destabilizing	0.014	N	0.325	neutral	N	0.377710405	None	None	N
L/W	0.9656	likely_pathogenic	0.964	pathogenic	-2.003	Highly Destabilizing	0.998	D	0.74	deleterious	None	None	None	None	N
L/Y	0.9751	likely_pathogenic	0.9761	pathogenic	-1.748	Destabilizing	0.978	D	0.717	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.