TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9007	27244;27245;27246	chr2:178713115;178713114;178713113	chr2:179577842;179577841;179577840
N2AB	8690	26293;26294;26295	chr2:178713115;178713114;178713113	chr2:179577842;179577841;179577840
N2A	7763	23512;23513;23514	chr2:178713115;178713114;178713113	chr2:179577842;179577841;179577840
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-75
• Domain position: 82
• Structural Position: 166
• Q(SASA): 0.1872
• 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/V	rs1456494692	0.116	0.998	N	0.779	0.387	0.631910935859	gnomAD-2.1.1	3.18E-05	None	None	None	None	N	None	1.14732E-04	0	None	0	0	None	0	None	0	0	0
D/V	rs1456494692	0.116	0.998	N	0.779	0.387	0.631910935859	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	4.82E-05	0	0	0	0	None	0	0	0	0	0
D/V	rs1456494692	0.116	0.998	N	0.779	0.387	0.631910935859	gnomAD-4.0.0	1.31404E-05	None	None	None	None	N	None	4.82369E-05	0	None	0	0	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
D/A	0.1366	likely_benign	0.1158	benign	-0.749	Destabilizing	0.978	D	0.641	neutral	N	0.406746099	None	None	N
D/C	0.6427	likely_pathogenic	0.6421	pathogenic	-0.271	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
D/E	0.2566	likely_benign	0.2245	benign	-0.668	Destabilizing	0.989	D	0.519	neutral	N	0.508699817	None	None	N
D/F	0.7114	likely_pathogenic	0.7129	pathogenic	-0.35	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
D/G	0.2124	likely_benign	0.2136	benign	-1.085	Destabilizing	0.989	D	0.594	neutral	D	0.529019161	None	None	N
D/H	0.359	ambiguous	0.3765	ambiguous	-0.569	Destabilizing	1.0	D	0.649	neutral	N	0.506407612	None	None	N
D/I	0.5037	ambiguous	0.4674	ambiguous	0.139	Stabilizing	0.999	D	0.805	deleterious	None	None	None	None	N
D/K	0.4115	ambiguous	0.3961	ambiguous	-0.265	Destabilizing	0.784	D	0.351	neutral	None	None	None	None	N
D/L	0.5402	ambiguous	0.511	ambiguous	0.139	Stabilizing	0.999	D	0.74	deleterious	None	None	None	None	N
D/M	0.7014	likely_pathogenic	0.6705	pathogenic	0.575	Stabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
D/N	0.1182	likely_benign	0.1297	benign	-0.73	Destabilizing	0.989	D	0.597	neutral	N	0.485643558	None	None	N
D/P	0.9733	likely_pathogenic	0.9759	pathogenic	-0.133	Destabilizing	0.999	D	0.665	neutral	None	None	None	None	N
D/Q	0.4092	ambiguous	0.3758	ambiguous	-0.632	Destabilizing	0.998	D	0.587	neutral	None	None	None	None	N
D/R	0.4345	ambiguous	0.4058	ambiguous	-0.087	Destabilizing	0.995	D	0.741	deleterious	None	None	None	None	N
D/S	0.0963	likely_benign	0.0977	benign	-0.987	Destabilizing	0.82	D	0.299	neutral	None	None	None	None	N
D/T	0.2804	likely_benign	0.257	benign	-0.707	Destabilizing	0.983	D	0.631	neutral	None	None	None	None	N
D/V	0.2816	likely_benign	0.2526	benign	-0.133	Destabilizing	0.998	D	0.779	deleterious	N	0.456654844	None	None	N
D/W	0.9403	likely_pathogenic	0.9396	pathogenic	-0.099	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
D/Y	0.3464	ambiguous	0.3561	ambiguous	-0.074	Destabilizing	0.999	D	0.801	deleterious	N	0.513409051	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.