TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26687	80284;80285;80286	chr2:178566073;178566072;178566071	chr2:179430800;179430799;179430798
N2AB	25046	75361;75362;75363	chr2:178566073;178566072;178566071	chr2:179430800;179430799;179430798
N2A	24119	72580;72581;72582	chr2:178566073;178566072;178566071	chr2:179430800;179430799;179430798
N2B	17622	53089;53090;53091	chr2:178566073;178566072;178566071	chr2:179430800;179430799;179430798
Novex-1	17747	53464;53465;53466	chr2:178566073;178566072;178566071	chr2:179430800;179430799;179430798
Novex-2	17814	53665;53666;53667	chr2:178566073;178566072;178566071	chr2:179430800;179430799;179430798
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: Fn3-82
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.0953
• 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/Q	None	None	1.0	D	0.897	0.755	0.620070164782	gnomAD-4.0.0	1.36855E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99556E-07	0	1.657E-05
P/S	None	None	0.999	D	0.865	0.714	0.587297536726	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	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	0.4073	ambiguous	0.4422	ambiguous	-2.311	Highly Destabilizing	0.982	D	0.82	deleterious	D	0.588851262	None	None	N
P/C	0.5722	likely_pathogenic	0.6052	pathogenic	-1.891	Destabilizing	1.0	D	0.929	deleterious	None	None	None	None	N
P/D	0.9992	likely_pathogenic	0.9993	pathogenic	-3.269	Highly Destabilizing	0.993	D	0.881	deleterious	None	None	None	None	N
P/E	0.9965	likely_pathogenic	0.9968	pathogenic	-2.998	Highly Destabilizing	0.996	D	0.881	deleterious	None	None	None	None	N
P/F	0.9967	likely_pathogenic	0.9965	pathogenic	-1.091	Destabilizing	1.0	D	0.945	deleterious	None	None	None	None	N
P/G	0.9729	likely_pathogenic	0.9795	pathogenic	-2.832	Highly Destabilizing	0.999	D	0.914	deleterious	None	None	None	None	N
P/H	0.9955	likely_pathogenic	0.9957	pathogenic	-2.63	Highly Destabilizing	1.0	D	0.929	deleterious	None	None	None	None	N
P/I	0.5843	likely_pathogenic	0.5784	pathogenic	-0.799	Destabilizing	0.984	D	0.803	deleterious	None	None	None	None	N
P/K	0.9983	likely_pathogenic	0.9984	pathogenic	-1.857	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
P/L	0.677	likely_pathogenic	0.6753	pathogenic	-0.799	Destabilizing	0.998	D	0.892	deleterious	D	0.634325174	None	None	N
P/M	0.9192	likely_pathogenic	0.9287	pathogenic	-1.18	Destabilizing	1.0	D	0.941	deleterious	None	None	None	None	N
P/N	0.9955	likely_pathogenic	0.9963	pathogenic	-2.397	Highly Destabilizing	0.999	D	0.933	deleterious	None	None	None	None	N
P/Q	0.9901	likely_pathogenic	0.9905	pathogenic	-2.1	Highly Destabilizing	1.0	D	0.897	deleterious	D	0.624806423	None	None	N
P/R	0.9937	likely_pathogenic	0.9932	pathogenic	-1.836	Destabilizing	1.0	D	0.938	deleterious	D	0.634526978	None	None	N
P/S	0.9062	likely_pathogenic	0.921	pathogenic	-2.859	Highly Destabilizing	0.999	D	0.865	deleterious	D	0.624806423	None	None	N
P/T	0.6924	likely_pathogenic	0.7198	pathogenic	-2.464	Highly Destabilizing	0.997	D	0.863	deleterious	D	0.608988866	None	None	N
P/V	0.2797	likely_benign	0.2995	benign	-1.287	Destabilizing	0.991	D	0.861	deleterious	None	None	None	None	N
P/W	0.9996	likely_pathogenic	0.9995	pathogenic	-1.687	Destabilizing	1.0	D	0.912	deleterious	None	None	None	None	N
P/Y	0.9989	likely_pathogenic	0.9988	pathogenic	-1.432	Destabilizing	1.0	D	0.949	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.