TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32775	98548;98549;98550	chr2:178539742;178539741;178539740	chr2:179404469;179404468;179404467
N2AB	31134	93625;93626;93627	chr2:178539742;178539741;178539740	chr2:179404469;179404468;179404467
N2A	30207	90844;90845;90846	chr2:178539742;178539741;178539740	chr2:179404469;179404468;179404467
N2B	23710	71353;71354;71355	chr2:178539742;178539741;178539740	chr2:179404469;179404468;179404467
Novex-1	23835	71728;71729;71730	chr2:178539742;178539741;178539740	chr2:179404469;179404468;179404467
Novex-2	23902	71929;71930;71931	chr2:178539742;178539741;178539740	chr2:179404469;179404468;179404467
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-155
• Domain position: 68
• Structural Position: 156
• Q(SASA): 0.1215
• 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/M	None	None	1.0	N	0.815	0.259	0.315903272564	gnomAD-4.0.0	6.84202E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.6564E-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
L/A	0.8533	likely_pathogenic	0.8662	pathogenic	-2.484	Highly Destabilizing	0.999	D	0.81	deleterious	None	None	None	None	N
L/C	0.8011	likely_pathogenic	0.8118	pathogenic	-1.783	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
L/D	0.9996	likely_pathogenic	0.9996	pathogenic	-2.581	Highly Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
L/E	0.9976	likely_pathogenic	0.9977	pathogenic	-2.346	Highly Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
L/F	0.686	likely_pathogenic	0.709	pathogenic	-1.513	Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
L/G	0.985	likely_pathogenic	0.9867	pathogenic	-3.053	Highly Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
L/H	0.993	likely_pathogenic	0.9935	pathogenic	-2.479	Highly Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
L/I	0.1675	likely_benign	0.1729	benign	-0.838	Destabilizing	0.999	D	0.747	deleterious	None	None	None	None	N
L/K	0.9962	likely_pathogenic	0.9959	pathogenic	-1.841	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
L/M	0.2751	likely_benign	0.28	benign	-0.772	Destabilizing	1.0	D	0.815	deleterious	N	0.502751627	None	None	N
L/N	0.9969	likely_pathogenic	0.9969	pathogenic	-2.19	Highly Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
L/P	0.9986	likely_pathogenic	0.9985	pathogenic	-1.367	Destabilizing	1.0	D	0.869	deleterious	N	0.484876413	None	None	N
L/Q	0.9901	likely_pathogenic	0.9899	pathogenic	-2.03	Highly Destabilizing	1.0	D	0.875	deleterious	N	0.484876413	None	None	N
L/R	0.9909	likely_pathogenic	0.9908	pathogenic	-1.612	Destabilizing	1.0	D	0.868	deleterious	N	0.484876413	None	None	N
L/S	0.9908	likely_pathogenic	0.9924	pathogenic	-2.942	Highly Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	N
L/T	0.9406	likely_pathogenic	0.9504	pathogenic	-2.545	Highly Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
L/V	0.1743	likely_benign	0.1988	benign	-1.367	Destabilizing	0.999	D	0.769	deleterious	N	0.45840063	None	None	N
L/W	0.9838	likely_pathogenic	0.9864	pathogenic	-1.873	Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
L/Y	0.9782	likely_pathogenic	0.9801	pathogenic	-1.57	Destabilizing	1.0	D	0.853	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.