TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34045	102358;102359;102360	chr2:178534482;178534481;178534480	chr2:179399209;179399208;179399207
N2AB	32404	97435;97436;97437	chr2:178534482;178534481;178534480	chr2:179399209;179399208;179399207
N2A	31477	94654;94655;94656	chr2:178534482;178534481;178534480	chr2:179399209;179399208;179399207
N2B	24980	75163;75164;75165	chr2:178534482;178534481;178534480	chr2:179399209;179399208;179399207
Novex-1	25105	75538;75539;75540	chr2:178534482;178534481;178534480	chr2:179399209;179399208;179399207
Novex-2	25172	75739;75740;75741	chr2:178534482;178534481;178534480	chr2:179399209;179399208;179399207
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Kinase-1
• Domain position: 233
• Q(SASA): 0.2371
• 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
E/D	None	None	None	N	None	0.312	0.431712495121	gnomAD-4.0.0	1.59171E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85814E-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
E/A	0.4745	ambiguous	0.4036	ambiguous	-0.984	Destabilizing	None	None	None	None	N	0.521303755	None	None	N
E/C	0.9737	likely_pathogenic	0.9628	pathogenic	-0.609	Destabilizing	None	None	None	None	None	None	None	None	N
E/D	0.5313	ambiguous	0.4772	ambiguous	-1.359	Destabilizing	None	None	None	None	N	0.503083354	None	None	N
E/F	0.9659	likely_pathogenic	0.9393	pathogenic	-0.592	Destabilizing	None	None	None	None	None	None	None	None	N
E/G	0.6251	likely_pathogenic	0.5685	pathogenic	-1.383	Destabilizing	None	None	None	None	N	0.519919675	None	None	N
E/H	0.8943	likely_pathogenic	0.8471	pathogenic	-1.07	Destabilizing	None	None	None	None	None	None	None	None	N
E/I	0.8782	likely_pathogenic	0.8252	pathogenic	0.123	Stabilizing	None	None	None	None	None	None	None	None	N
E/K	0.6366	likely_pathogenic	0.5451	ambiguous	-1.311	Destabilizing	None	None	None	None	N	0.488619299	None	None	N
E/L	0.8693	likely_pathogenic	0.8116	pathogenic	0.123	Stabilizing	None	None	None	None	None	None	None	None	N
E/M	0.8975	likely_pathogenic	0.8636	pathogenic	0.782	Stabilizing	None	None	None	None	None	None	None	None	N
E/N	0.831	likely_pathogenic	0.78	pathogenic	-1.629	Destabilizing	None	None	None	None	None	None	None	None	N
E/P	0.8985	likely_pathogenic	0.8763	pathogenic	-0.225	Destabilizing	None	None	None	None	None	None	None	None	N
E/Q	0.4712	ambiguous	0.4109	ambiguous	-1.404	Destabilizing	None	None	None	None	D	0.522362548	None	None	N
E/R	0.7235	likely_pathogenic	0.6447	pathogenic	-1.113	Destabilizing	None	None	None	None	None	None	None	None	N
E/S	0.6834	likely_pathogenic	0.6259	pathogenic	-2.042	Highly Destabilizing	None	None	None	None	None	None	None	None	N
E/T	0.7288	likely_pathogenic	0.6568	pathogenic	-1.716	Destabilizing	None	None	None	None	None	None	None	None	N
E/V	0.7394	likely_pathogenic	0.6673	pathogenic	-0.225	Destabilizing	None	None	None	None	N	0.500673621	None	None	N
E/W	0.9888	likely_pathogenic	0.9807	pathogenic	-0.53	Destabilizing	None	None	None	None	None	None	None	None	N
E/Y	0.9353	likely_pathogenic	0.8948	pathogenic	-0.433	Destabilizing	None	None	None	None	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.