TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	10155	30688;30689;30690	chr2:178702216;178702215;178702214	chr2:179566943;179566942;179566941
N2AB	9838	29737;29738;29739	chr2:178702216;178702215;178702214	chr2:179566943;179566942;179566941
N2A	8911	26956;26957;26958	chr2:178702216;178702215;178702214	chr2:179566943;179566942;179566941
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-86
• Domain position: 78
• Structural Position: 162
• Q(SASA): 0.0678
• 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	1.0	None	0.797	0.522	0.801471871174	gnomAD-4.0.0	1.59085E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85745E-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	0.858	likely_pathogenic	0.8419	pathogenic	-0.381	Destabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	N
P/C	0.994	likely_pathogenic	0.9939	pathogenic	-0.816	Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
P/D	0.9303	likely_pathogenic	0.9253	pathogenic	-0.415	Destabilizing	1.0	D	0.778	deleterious	None	None	None	None	N
P/E	0.9322	likely_pathogenic	0.9308	pathogenic	-0.525	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	N
P/F	0.9924	likely_pathogenic	0.9924	pathogenic	-0.689	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
P/G	0.9022	likely_pathogenic	0.8991	pathogenic	-0.459	Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	N
P/H	0.9429	likely_pathogenic	0.9407	pathogenic	0.01	Stabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
P/I	0.9768	likely_pathogenic	0.9763	pathogenic	-0.315	Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	N
P/K	0.9606	likely_pathogenic	0.9572	pathogenic	-0.458	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
P/L	0.929	likely_pathogenic	0.9199	pathogenic	-0.315	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
P/M	0.9806	likely_pathogenic	0.9794	pathogenic	-0.595	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
P/N	0.9355	likely_pathogenic	0.9321	pathogenic	-0.283	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
P/Q	0.9421	likely_pathogenic	0.9377	pathogenic	-0.494	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
P/R	0.9296	likely_pathogenic	0.923	pathogenic	0.025	Stabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
P/S	0.9056	likely_pathogenic	0.8971	pathogenic	-0.588	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
P/T	0.8792	likely_pathogenic	0.8702	pathogenic	-0.605	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
P/V	0.9477	likely_pathogenic	0.9456	pathogenic	-0.308	Destabilizing	1.0	D	0.778	deleterious	None	None	None	None	N
P/W	0.9943	likely_pathogenic	0.9938	pathogenic	-0.751	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
P/Y	0.9807	likely_pathogenic	0.9801	pathogenic	-0.478	Destabilizing	1.0	D	0.821	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.