TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7683	23272;23273;23274	chr2:178720972;178720971;178720970	chr2:179585699;179585698;179585697
N2AB	7366	22321;22322;22323	chr2:178720972;178720971;178720970	chr2:179585699;179585698;179585697
N2A	6439	19540;19541;19542	chr2:178720972;178720971;178720970	chr2:179585699;179585698;179585697
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-61
• Domain position: 76
• Structural Position: 158
• Q(SASA): 0.0903
• 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/P	rs2078270258	None	1.0	D	0.879	0.65	0.790187556284	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
A/P	rs2078270258	None	1.0	D	0.879	0.65	0.790187556284	gnomAD-4.0.0	6.57142E-06	None	None	None	None	N	None	2.41243E-05	0	None	0	0	None	0	0	0	0	0
A/S	None	None	0.995	D	0.629	0.515	0.648076967581	gnomAD-4.0.0	1.60929E-06	None	None	None	None	N	None	0	0	None	0	2.78738E-05	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
A/C	0.9279	likely_pathogenic	0.9292	pathogenic	-1.708	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
A/D	0.9959	likely_pathogenic	0.9963	pathogenic	-3.0	Highly Destabilizing	1.0	D	0.867	deleterious	D	0.651073184	None	None	N
A/E	0.9913	likely_pathogenic	0.9913	pathogenic	-2.835	Highly Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
A/F	0.9413	likely_pathogenic	0.9475	pathogenic	-0.794	Destabilizing	0.999	D	0.884	deleterious	None	None	None	None	N
A/G	0.4002	ambiguous	0.473	ambiguous	-1.766	Destabilizing	0.904	D	0.623	neutral	D	0.582413167	None	None	N
A/H	0.9971	likely_pathogenic	0.997	pathogenic	-1.966	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
A/I	0.632	likely_pathogenic	0.6824	pathogenic	-0.208	Destabilizing	0.997	D	0.756	deleterious	None	None	None	None	N
A/K	0.9982	likely_pathogenic	0.9981	pathogenic	-1.479	Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
A/L	0.6824	likely_pathogenic	0.712	pathogenic	-0.208	Destabilizing	0.992	D	0.694	prob.neutral	None	None	None	None	N
A/M	0.8333	likely_pathogenic	0.8432	pathogenic	-0.568	Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
A/N	0.9891	likely_pathogenic	0.9904	pathogenic	-1.821	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
A/P	0.9925	likely_pathogenic	0.9941	pathogenic	-0.546	Destabilizing	1.0	D	0.879	deleterious	D	0.634852018	None	None	N
A/Q	0.9891	likely_pathogenic	0.9887	pathogenic	-1.694	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
A/R	0.9933	likely_pathogenic	0.9924	pathogenic	-1.433	Destabilizing	1.0	D	0.872	deleterious	None	None	None	None	N
A/S	0.4998	ambiguous	0.5359	ambiguous	-2.155	Highly Destabilizing	0.995	D	0.629	neutral	D	0.594980419	None	None	N
A/T	0.5808	likely_pathogenic	0.641	pathogenic	-1.885	Destabilizing	0.999	D	0.697	prob.neutral	D	0.608708494	None	None	N
A/V	0.298	likely_benign	0.3477	ambiguous	-0.546	Destabilizing	0.553	D	0.4	neutral	D	0.527640656	None	None	N
A/W	0.998	likely_pathogenic	0.9976	pathogenic	-1.513	Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
A/Y	0.9894	likely_pathogenic	0.9893	pathogenic	-1.069	Destabilizing	1.0	D	0.89	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.