TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9301	28126;28127;28128	chr2:178711335;178711334;178711333	chr2:179576062;179576061;179576060
N2AB	8984	27175;27176;27177	chr2:178711335;178711334;178711333	chr2:179576062;179576061;179576060
N2A	8057	24394;24395;24396	chr2:178711335;178711334;178711333	chr2:179576062;179576061;179576060
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: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-79
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.1762
• 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	rs372056758	-0.092	1.0	D	0.892	0.815	None	gnomAD-2.1.1	4.1E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.01E-06	0
P/L	rs372056758	-0.092	1.0	D	0.892	0.815	None	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	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	0.5885	likely_pathogenic	0.6777	pathogenic	-1.378	Destabilizing	1.0	D	0.842	deleterious	D	0.631407038	None	None	N
P/C	0.9723	likely_pathogenic	0.9835	pathogenic	-1.488	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
P/D	0.9988	likely_pathogenic	0.9993	pathogenic	-1.037	Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
P/E	0.9957	likely_pathogenic	0.9975	pathogenic	-1.042	Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	N
P/F	0.9956	likely_pathogenic	0.997	pathogenic	-1.351	Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
P/G	0.9773	likely_pathogenic	0.9871	pathogenic	-1.644	Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
P/H	0.9915	likely_pathogenic	0.9948	pathogenic	-1.184	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
P/I	0.9288	likely_pathogenic	0.9507	pathogenic	-0.751	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
P/K	0.9963	likely_pathogenic	0.998	pathogenic	-0.931	Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	N
P/L	0.8309	likely_pathogenic	0.8716	pathogenic	-0.751	Destabilizing	1.0	D	0.892	deleterious	D	0.625310036	None	None	N
P/M	0.9796	likely_pathogenic	0.985	pathogenic	-0.801	Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
P/N	0.9966	likely_pathogenic	0.9978	pathogenic	-0.817	Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
P/Q	0.9872	likely_pathogenic	0.9926	pathogenic	-1.022	Destabilizing	1.0	D	0.883	deleterious	D	0.657550562	None	None	N
P/R	0.9845	likely_pathogenic	0.9917	pathogenic	-0.533	Destabilizing	1.0	D	0.891	deleterious	D	0.657550562	None	None	N
P/S	0.9409	likely_pathogenic	0.9603	pathogenic	-1.424	Destabilizing	1.0	D	0.894	deleterious	D	0.631608842	None	None	N
P/T	0.9101	likely_pathogenic	0.9392	pathogenic	-1.314	Destabilizing	1.0	D	0.89	deleterious	D	0.657348758	None	None	N
P/V	0.8262	likely_pathogenic	0.8672	pathogenic	-0.928	Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
P/W	0.9992	likely_pathogenic	0.9996	pathogenic	-1.435	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
P/Y	0.9975	likely_pathogenic	0.9984	pathogenic	-1.095	Destabilizing	1.0	D	0.9	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.