TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28255	84988;84989;84990	chr2:178561369;178561368;178561367	chr2:179426096;179426095;179426094
N2AB	26614	80065;80066;80067	chr2:178561369;178561368;178561367	chr2:179426096;179426095;179426094
N2A	25687	77284;77285;77286	chr2:178561369;178561368;178561367	chr2:179426096;179426095;179426094
N2B	19190	57793;57794;57795	chr2:178561369;178561368;178561367	chr2:179426096;179426095;179426094
Novex-1	19315	58168;58169;58170	chr2:178561369;178561368;178561367	chr2:179426096;179426095;179426094
Novex-2	19382	58369;58370;58371	chr2:178561369;178561368;178561367	chr2:179426096;179426095;179426094
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: Fn3-94
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.1957
• 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	rs1703598147	None	0.999	D	0.848	0.495	0.782479200985	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	None	0	0	0	0	0
P/S	rs1703599575	None	0.905	N	0.453	0.334	0.249502417897	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	6.57E-05	0	0	0	None	0	0	0	0	0
P/S	rs1703599575	None	0.905	N	0.453	0.334	0.249502417897	gnomAD-4.0.0	6.5799E-06	None	None	None	None	N	None	0	6.56513E-05	None	0	0	None	0	0	0	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	0.0972	likely_benign	0.0793	benign	-1.42	Destabilizing	0.992	D	0.75	deleterious	N	0.492521565	None	None	N
P/C	0.5015	ambiguous	0.5133	ambiguous	-1.118	Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
P/D	0.8802	likely_pathogenic	0.862	pathogenic	-2.395	Highly Destabilizing	0.999	D	0.839	deleterious	None	None	None	None	N
P/E	0.5559	ambiguous	0.5326	ambiguous	-2.426	Highly Destabilizing	0.999	D	0.837	deleterious	None	None	None	None	N
P/F	0.6723	likely_pathogenic	0.6673	pathogenic	-1.372	Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
P/G	0.5205	ambiguous	0.4994	ambiguous	-1.688	Destabilizing	0.997	D	0.807	deleterious	None	None	None	None	N
P/H	0.3383	likely_benign	0.3502	ambiguous	-1.287	Destabilizing	1.0	D	0.883	deleterious	D	0.525711684	None	None	N
P/I	0.4279	ambiguous	0.4268	ambiguous	-0.777	Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	N
P/K	0.3496	ambiguous	0.3481	ambiguous	-1.188	Destabilizing	0.999	D	0.835	deleterious	None	None	None	None	N
P/L	0.2372	likely_benign	0.2477	benign	-0.777	Destabilizing	0.999	D	0.848	deleterious	D	0.536979084	None	None	N
P/M	0.4542	ambiguous	0.4787	ambiguous	-0.51	Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
P/N	0.6885	likely_pathogenic	0.6721	pathogenic	-1.118	Destabilizing	0.999	D	0.879	deleterious	None	None	None	None	N
P/Q	0.2638	likely_benign	0.27	benign	-1.402	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
P/R	0.2177	likely_benign	0.2216	benign	-0.622	Destabilizing	0.999	D	0.891	deleterious	N	0.50361773	None	None	N
P/S	0.2098	likely_benign	0.1776	benign	-1.441	Destabilizing	0.905	D	0.453	neutral	N	0.50400935	None	None	N
P/T	0.226	likely_benign	0.2122	benign	-1.383	Destabilizing	0.992	D	0.798	deleterious	N	0.5116199	None	None	N
P/V	0.3092	likely_benign	0.2941	benign	-0.96	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
P/W	0.8308	likely_pathogenic	0.8465	pathogenic	-1.602	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
P/Y	0.6756	likely_pathogenic	0.6668	pathogenic	-1.284	Destabilizing	1.0	D	0.887	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.