TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7831	23716;23717;23718	chr2:178720151;178720150;178720149	chr2:179584878;179584877;179584876
N2AB	7514	22765;22766;22767	chr2:178720151;178720150;178720149	chr2:179584878;179584877;179584876
N2A	6587	19984;19985;19986	chr2:178720151;178720150;178720149	chr2:179584878;179584877;179584876
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: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-63
• Domain position: 37
• Structural Position: 51
• Q(SASA): 0.5638
• 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
D/H	rs1220028372	0.112	0.652	N	0.525	0.36	0.226586394389	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
D/H	rs1220028372	0.112	0.652	N	0.525	0.36	0.226586394389	gnomAD-4.0.0	3.42122E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	1.7343E-04	3.59804E-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
D/A	0.4635	ambiguous	0.4061	ambiguous	-0.567	Destabilizing	0.05	N	0.527	neutral	N	0.487539893	None	None	N
D/C	0.894	likely_pathogenic	0.8626	pathogenic	-0.235	Destabilizing	0.767	D	0.62	neutral	None	None	None	None	N
D/E	0.2319	likely_benign	0.172	benign	-0.506	Destabilizing	0.006	N	0.407	neutral	N	0.459761173	None	None	N
D/F	0.8606	likely_pathogenic	0.8292	pathogenic	-0.134	Destabilizing	0.976	D	0.617	neutral	None	None	None	None	N
D/G	0.1954	likely_benign	0.1824	benign	-0.887	Destabilizing	None	N	0.317	neutral	N	0.483902135	None	None	N
D/H	0.6617	likely_pathogenic	0.6244	pathogenic	-0.349	Destabilizing	0.652	D	0.525	neutral	N	0.502036524	None	None	N
D/I	0.8228	likely_pathogenic	0.7693	pathogenic	0.269	Stabilizing	0.781	D	0.636	neutral	None	None	None	None	N
D/K	0.7795	likely_pathogenic	0.7247	pathogenic	-0.244	Destabilizing	0.469	N	0.531	neutral	None	None	None	None	N
D/L	0.7549	likely_pathogenic	0.705	pathogenic	0.269	Stabilizing	0.638	D	0.646	neutral	None	None	None	None	N
D/M	0.8973	likely_pathogenic	0.8587	pathogenic	0.589	Stabilizing	0.939	D	0.622	neutral	None	None	None	None	N
D/N	0.1696	likely_benign	0.163	benign	-0.682	Destabilizing	None	N	0.251	neutral	N	0.493937356	None	None	N
D/P	0.9436	likely_pathogenic	0.9194	pathogenic	0.015	Stabilizing	0.066	N	0.551	neutral	None	None	None	None	N
D/Q	0.6584	likely_pathogenic	0.5856	pathogenic	-0.564	Destabilizing	0.397	N	0.501	neutral	None	None	None	None	N
D/R	0.786	likely_pathogenic	0.7466	pathogenic	-0.04	Destabilizing	0.638	D	0.575	neutral	None	None	None	None	N
D/S	0.2842	likely_benign	0.2523	benign	-0.888	Destabilizing	0.066	N	0.432	neutral	None	None	None	None	N
D/T	0.6624	likely_pathogenic	0.5832	pathogenic	-0.628	Destabilizing	0.099	N	0.52	neutral	None	None	None	None	N
D/V	0.6049	likely_pathogenic	0.5406	ambiguous	0.015	Stabilizing	0.321	N	0.647	neutral	N	0.513810903	None	None	N
D/W	0.9638	likely_pathogenic	0.954	pathogenic	0.09	Stabilizing	0.976	D	0.613	neutral	None	None	None	None	N
D/Y	0.5192	ambiguous	0.4944	ambiguous	0.112	Stabilizing	0.969	D	0.615	neutral	N	0.520394268	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.