TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8084	24475;24476;24477	chr2:178718950;178718949;178718948	chr2:179583677;179583676;179583675
N2AB	7767	23524;23525;23526	chr2:178718950;178718949;178718948	chr2:179583677;179583676;179583675
N2A	6840	20743;20744;20745	chr2:178718950;178718949;178718948	chr2:179583677;179583676;179583675
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-66
• Domain position: 7
• Structural Position: 8
• Q(SASA): 0.1666
• 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/H	None	None	1.0	D	0.875	0.385	0.437420747294	gnomAD-4.0.0	1.60295E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.04062E-05

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	0.4006	ambiguous	0.3131	benign	-1.549	Destabilizing	0.998	D	0.626	neutral	N	0.500982886	None	None	N
P/C	0.9537	likely_pathogenic	0.9253	pathogenic	-1.285	Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
P/D	0.9833	likely_pathogenic	0.9722	pathogenic	-0.902	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
P/E	0.9427	likely_pathogenic	0.909	pathogenic	-0.833	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
P/F	0.9645	likely_pathogenic	0.9437	pathogenic	-1.132	Destabilizing	1.0	D	0.896	deleterious	None	None	None	None	N
P/G	0.8932	likely_pathogenic	0.8397	pathogenic	-1.938	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
P/H	0.9326	likely_pathogenic	0.8916	pathogenic	-1.489	Destabilizing	1.0	D	0.875	deleterious	D	0.525127528	None	None	N
P/I	0.8085	likely_pathogenic	0.7468	pathogenic	-0.551	Destabilizing	0.998	D	0.847	deleterious	None	None	None	None	N
P/K	0.9614	likely_pathogenic	0.9326	pathogenic	-0.964	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
P/L	0.4854	ambiguous	0.3982	ambiguous	-0.551	Destabilizing	0.64	D	0.631	neutral	N	0.451271115	None	None	N
P/M	0.796	likely_pathogenic	0.7433	pathogenic	-0.591	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
P/N	0.9732	likely_pathogenic	0.9549	pathogenic	-0.864	Destabilizing	1.0	D	0.876	deleterious	None	None	None	None	N
P/Q	0.8892	likely_pathogenic	0.8161	pathogenic	-0.921	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
P/R	0.9147	likely_pathogenic	0.8542	pathogenic	-0.693	Destabilizing	1.0	D	0.873	deleterious	D	0.524620549	None	None	N
P/S	0.7909	likely_pathogenic	0.6953	pathogenic	-1.591	Destabilizing	1.0	D	0.767	deleterious	N	0.492019664	None	None	N
P/T	0.63	likely_pathogenic	0.5371	ambiguous	-1.385	Destabilizing	0.999	D	0.767	deleterious	N	0.497615524	None	None	N
P/V	0.6888	likely_pathogenic	0.6083	pathogenic	-0.85	Destabilizing	0.998	D	0.768	deleterious	None	None	None	None	N
P/W	0.9891	likely_pathogenic	0.9799	pathogenic	-1.319	Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
P/Y	0.9842	likely_pathogenic	0.9712	pathogenic	-0.983	Destabilizing	1.0	D	0.895	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.