TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9318	28177;28178;28179	chr2:178711284;178711283;178711282	chr2:179576011;179576010;179576009
N2AB	9001	27226;27227;27228	chr2:178711284;178711283;178711282	chr2:179576011;179576010;179576009
N2A	8074	24445;24446;24447	chr2:178711284;178711283;178711282	chr2:179576011;179576010;179576009
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: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-79
• Domain position: 18
• Structural Position: 28
• Q(SASA): 0.2087
• 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
V/F	rs368920200	-1.094	0.968	None	0.752	0.243	None	gnomAD-2.1.1	8.04E-06	None	None	None	None	N	None	1.29216E-04	0	None	0	0	None	0	None	0	0	0
V/F	rs368920200	-1.094	0.968	None	0.752	0.243	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
V/F	rs368920200	-1.094	0.968	None	0.752	0.243	None	gnomAD-4.0.0	2.02987E-06	None	None	None	None	N	None	3.49406E-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
V/A	0.1929	likely_benign	0.2493	benign	-1.782	Destabilizing	0.64	D	0.507	neutral	None	None	None	None	N
V/C	0.893	likely_pathogenic	0.9089	pathogenic	-1.432	Destabilizing	0.999	D	0.719	prob.delet.	None	None	None	None	N
V/D	0.9442	likely_pathogenic	0.9668	pathogenic	-1.79	Destabilizing	0.968	D	0.791	deleterious	None	None	None	None	N
V/E	0.8757	likely_pathogenic	0.91	pathogenic	-1.632	Destabilizing	0.976	D	0.762	deleterious	None	None	None	None	N
V/F	0.4909	ambiguous	0.5851	pathogenic	-1.106	Destabilizing	0.968	D	0.752	deleterious	None	None	None	None	N
V/G	0.574	likely_pathogenic	0.6719	pathogenic	-2.272	Highly Destabilizing	0.896	D	0.754	deleterious	None	None	None	None	N
V/H	0.9498	likely_pathogenic	0.9634	pathogenic	-1.891	Destabilizing	0.999	D	0.782	deleterious	None	None	None	None	N
V/I	0.0879	likely_benign	0.1003	benign	-0.46	Destabilizing	0.011	N	0.191	neutral	None	None	None	None	N
V/K	0.8969	likely_pathogenic	0.9209	pathogenic	-1.487	Destabilizing	0.976	D	0.758	deleterious	None	None	None	None	N
V/L	0.3356	likely_benign	0.408	ambiguous	-0.46	Destabilizing	0.64	D	0.439	neutral	None	None	None	None	N
V/M	0.2557	likely_benign	0.304	benign	-0.506	Destabilizing	0.976	D	0.617	neutral	None	None	None	None	N
V/N	0.8485	likely_pathogenic	0.8914	pathogenic	-1.622	Destabilizing	0.976	D	0.803	deleterious	None	None	None	None	N
V/P	0.9714	likely_pathogenic	0.9863	pathogenic	-0.868	Destabilizing	0.988	D	0.787	deleterious	None	None	None	None	N
V/Q	0.8553	likely_pathogenic	0.8901	pathogenic	-1.544	Destabilizing	0.988	D	0.795	deleterious	None	None	None	None	N
V/R	0.8346	likely_pathogenic	0.8674	pathogenic	-1.246	Destabilizing	0.988	D	0.823	deleterious	None	None	None	None	N
V/S	0.5109	ambiguous	0.5907	pathogenic	-2.29	Highly Destabilizing	0.307	N	0.435	neutral	None	None	None	None	N
V/T	0.2541	likely_benign	0.2933	benign	-1.981	Destabilizing	0.851	D	0.568	neutral	None	None	None	None	N
V/W	0.9814	likely_pathogenic	0.9893	pathogenic	-1.476	Destabilizing	0.999	D	0.779	deleterious	None	None	None	None	N
V/Y	0.9213	likely_pathogenic	0.9455	pathogenic	-1.096	Destabilizing	0.996	D	0.762	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.