TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7708	23347;23348;23349	chr2:178720640;178720639;178720638	chr2:179585367;179585366;179585365
N2AB	7391	22396;22397;22398	chr2:178720640;178720639;178720638	chr2:179585367;179585366;179585365
N2A	6464	19615;19616;19617	chr2:178720640;178720639;178720638	chr2:179585367;179585366;179585365
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: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Ig-62
• Domain position: 7
• Structural Position: 8
• Q(SASA): 0.2656
• 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
P/L	None	None	0.365	N	0.441	0.222	0.365317461125	gnomAD-4.0.0	1.38223E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.80818E-06	0	0
P/T	None	None	0.994	N	0.703	0.349	0.312306559268	gnomAD-4.0.0	1.63565E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.91344E-05	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
P/A	0.305	likely_benign	0.2691	benign	-1.427	Destabilizing	0.968	D	0.522	neutral	N	0.477611939	None	None	N
P/C	0.8793	likely_pathogenic	0.8488	pathogenic	-0.766	Destabilizing	0.999	D	0.781	deleterious	None	None	None	None	N
P/D	0.9777	likely_pathogenic	0.9738	pathogenic	-1.377	Destabilizing	0.99	D	0.755	deleterious	None	None	None	None	N
P/E	0.9437	likely_pathogenic	0.9323	pathogenic	-1.408	Destabilizing	0.994	D	0.742	deleterious	None	None	None	None	N
P/F	0.8876	likely_pathogenic	0.8705	pathogenic	-1.24	Destabilizing	0.999	D	0.793	deleterious	None	None	None	None	N
P/G	0.8357	likely_pathogenic	0.8075	pathogenic	-1.719	Destabilizing	0.999	D	0.725	prob.delet.	None	None	None	None	N
P/H	0.8956	likely_pathogenic	0.878	pathogenic	-1.439	Destabilizing	1.0	D	0.753	deleterious	N	0.491716949	None	None	N
P/I	0.5701	likely_pathogenic	0.5314	ambiguous	-0.732	Destabilizing	0.998	D	0.736	prob.delet.	None	None	None	None	N
P/K	0.963	likely_pathogenic	0.9546	pathogenic	-1.206	Destabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	N
P/L	0.2823	likely_benign	0.2429	benign	-0.732	Destabilizing	0.365	N	0.441	neutral	N	0.426346927	None	None	N
P/M	0.6521	likely_pathogenic	0.6051	pathogenic	-0.431	Destabilizing	0.999	D	0.768	deleterious	None	None	None	None	N
P/N	0.9412	likely_pathogenic	0.9272	pathogenic	-0.869	Destabilizing	0.998	D	0.776	deleterious	None	None	None	None	N
P/Q	0.8629	likely_pathogenic	0.8385	pathogenic	-1.077	Destabilizing	0.999	D	0.757	deleterious	None	None	None	None	N
P/R	0.9235	likely_pathogenic	0.9108	pathogenic	-0.695	Destabilizing	1.0	D	0.773	deleterious	N	0.49120997	None	None	N
P/S	0.7519	likely_pathogenic	0.7102	pathogenic	-1.306	Destabilizing	0.999	D	0.709	prob.delet.	N	0.469636221	None	None	N
P/T	0.5263	ambiguous	0.4603	ambiguous	-1.237	Destabilizing	0.994	D	0.703	prob.neutral	N	0.481157111	None	None	N
P/V	0.4567	ambiguous	0.4167	ambiguous	-0.929	Destabilizing	0.955	D	0.625	neutral	None	None	None	None	N
P/W	0.9827	likely_pathogenic	0.9784	pathogenic	-1.441	Destabilizing	1.0	D	0.752	deleterious	None	None	None	None	N
P/Y	0.9445	likely_pathogenic	0.9347	pathogenic	-1.161	Destabilizing	1.0	D	0.792	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.