TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5092	15499;15500;15501	chr2:178734550;178734549;178734548	chr2:179599277;179599276;179599275
N2AB	4775	14548;14549;14550	chr2:178734550;178734549;178734548	chr2:179599277;179599276;179599275
N2A	3848	11767;11768;11769	chr2:178734550;178734549;178734548	chr2:179599277;179599276;179599275
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: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-34
• Domain position: 18
• Structural Position: 28
• Q(SASA): 0.1208
• 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
A/T	rs765723566	-1.108	0.211	N	0.387	0.359	0.331619326243	gnomAD-2.1.1	2.08E-05	None	None	None	None	N	None	0	0	None	0	0	None	1.7534E-04	None	0	0	0
A/T	rs765723566	-1.108	0.211	N	0.387	0.359	0.331619326243	gnomAD-4.0.0	1.29085E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.17151E-04	0
A/V	None	None	0.211	N	0.389	0.292	0.411531665326	gnomAD-4.0.0	1.61129E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.89675E-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
A/C	0.599	likely_pathogenic	0.5074	ambiguous	-0.918	Destabilizing	0.999	D	0.656	neutral	None	None	None	None	N
A/D	0.9084	likely_pathogenic	0.8464	pathogenic	-1.491	Destabilizing	0.968	D	0.805	deleterious	D	0.745456411	None	None	N
A/E	0.8501	likely_pathogenic	0.766	pathogenic	-1.373	Destabilizing	0.976	D	0.806	deleterious	None	None	None	None	N
A/F	0.6463	likely_pathogenic	0.539	ambiguous	-0.819	Destabilizing	0.988	D	0.803	deleterious	None	None	None	None	N
A/G	0.297	likely_benign	0.2274	benign	-1.406	Destabilizing	0.896	D	0.583	neutral	D	0.617204423	None	None	N
A/H	0.8659	likely_pathogenic	0.7952	pathogenic	-1.773	Destabilizing	0.999	D	0.785	deleterious	None	None	None	None	N
A/I	0.378	ambiguous	0.3023	benign	0.094	Stabilizing	0.851	D	0.763	deleterious	None	None	None	None	N
A/K	0.9165	likely_pathogenic	0.8597	pathogenic	-1.146	Destabilizing	0.976	D	0.801	deleterious	None	None	None	None	N
A/L	0.3962	ambiguous	0.3061	benign	0.094	Stabilizing	0.851	D	0.665	neutral	None	None	None	None	N
A/M	0.424	ambiguous	0.3397	benign	0.026	Stabilizing	0.997	D	0.764	deleterious	None	None	None	None	N
A/N	0.7941	likely_pathogenic	0.6848	pathogenic	-1.135	Destabilizing	0.976	D	0.811	deleterious	None	None	None	None	N
A/P	0.9546	likely_pathogenic	0.9378	pathogenic	-0.219	Destabilizing	0.059	N	0.438	neutral	D	0.707686558	None	None	N
A/Q	0.8011	likely_pathogenic	0.7114	pathogenic	-1.053	Destabilizing	0.988	D	0.783	deleterious	None	None	None	None	N
A/R	0.8573	likely_pathogenic	0.7857	pathogenic	-1.128	Destabilizing	0.988	D	0.814	deleterious	None	None	None	None	N
A/S	0.1755	likely_benign	0.1506	benign	-1.601	Destabilizing	0.811	D	0.567	neutral	D	0.656579758	None	None	N
A/T	0.1477	likely_benign	0.1242	benign	-1.349	Destabilizing	0.211	N	0.387	neutral	N	0.519758082	None	None	N
A/V	0.1593	likely_benign	0.1347	benign	-0.219	Destabilizing	0.211	N	0.389	neutral	N	0.439827817	None	None	N
A/W	0.9572	likely_pathogenic	0.9259	pathogenic	-1.421	Destabilizing	0.999	D	0.779	deleterious	None	None	None	None	N
A/Y	0.8094	likely_pathogenic	0.7363	pathogenic	-0.879	Destabilizing	0.996	D	0.807	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.