TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23372	70339;70340;70341	chr2:178576018;178576017;178576016	chr2:179440745;179440744;179440743
N2AB	21731	65416;65417;65418	chr2:178576018;178576017;178576016	chr2:179440745;179440744;179440743
N2A	20804	62635;62636;62637	chr2:178576018;178576017;178576016	chr2:179440745;179440744;179440743
N2B	14307	43144;43145;43146	chr2:178576018;178576017;178576016	chr2:179440745;179440744;179440743
Novex-1	14432	43519;43520;43521	chr2:178576018;178576017;178576016	chr2:179440745;179440744;179440743
Novex-2	14499	43720;43721;43722	chr2:178576018;178576017;178576016	chr2:179440745;179440744;179440743
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-129
• Domain position: 28
• Structural Position: 42
• Q(SASA): 0.3522
• Predicted PPI site: I

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	rs1709955188	None	1.0	D	0.781	0.685	0.864968170662	gnomAD-4.0.0	1.59332E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86293E-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	0.904	likely_pathogenic	0.9443	pathogenic	-0.446	Destabilizing	1.0	D	0.727	prob.delet.	D	0.545326645	None	None	I
P/C	0.9899	likely_pathogenic	0.9952	pathogenic	-0.437	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	I
P/D	0.9849	likely_pathogenic	0.9926	pathogenic	-0.531	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	I
P/E	0.9798	likely_pathogenic	0.9899	pathogenic	-0.658	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	I
P/F	0.9926	likely_pathogenic	0.9971	pathogenic	-0.782	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	I
P/G	0.9725	likely_pathogenic	0.9845	pathogenic	-0.563	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	I
P/H	0.9688	likely_pathogenic	0.9848	pathogenic	-0.243	Destabilizing	1.0	D	0.807	deleterious	D	0.614100078	None	None	I
P/I	0.9562	likely_pathogenic	0.9781	pathogenic	-0.29	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	I
P/K	0.9767	likely_pathogenic	0.9869	pathogenic	-0.469	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	I
P/L	0.8892	likely_pathogenic	0.9387	pathogenic	-0.29	Destabilizing	1.0	D	0.781	deleterious	D	0.598080717	None	None	I
P/M	0.9694	likely_pathogenic	0.9838	pathogenic	-0.297	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	I
P/N	0.9779	likely_pathogenic	0.9882	pathogenic	-0.1	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	I
P/Q	0.9697	likely_pathogenic	0.9839	pathogenic	-0.378	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	I
P/R	0.9584	likely_pathogenic	0.9768	pathogenic	0.068	Stabilizing	1.0	D	0.815	deleterious	D	0.613696469	None	None	I
P/S	0.9663	likely_pathogenic	0.9827	pathogenic	-0.38	Destabilizing	1.0	D	0.765	deleterious	D	0.556175971	None	None	I
P/T	0.9209	likely_pathogenic	0.9553	pathogenic	-0.417	Destabilizing	1.0	D	0.761	deleterious	D	0.613696469	None	None	I
P/V	0.9252	likely_pathogenic	0.9571	pathogenic	-0.308	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	I
P/W	0.9969	likely_pathogenic	0.9987	pathogenic	-0.88	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	I
P/Y	0.9894	likely_pathogenic	0.9955	pathogenic	-0.578	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	I

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.