TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7472	22639;22640;22641	chr2:178722373;178722372;178722371	chr2:179587100;179587099;179587098
N2AB	7155	21688;21689;21690	chr2:178722373;178722372;178722371	chr2:179587100;179587099;179587098
N2A	6228	18907;18908;18909	chr2:178722373;178722372;178722371	chr2:179587100;179587099;179587098
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: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-59
• Domain position: 54
• Structural Position: 134
• Q(SASA): 0.3318
• 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
N/D	rs1174856533	None	0.979	N	0.579	0.32	0.362758974969	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
N/D	rs1174856533	None	0.979	N	0.579	0.32	0.362758974969	gnomAD-4.0.0	2.56343E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.78835E-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
N/A	0.5327	ambiguous	0.4648	ambiguous	-0.945	Destabilizing	0.908	D	0.687	prob.neutral	None	None	None	None	N
N/C	0.6119	likely_pathogenic	0.5788	pathogenic	-0.099	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
N/D	0.2248	likely_benign	0.1901	benign	-0.555	Destabilizing	0.979	D	0.579	neutral	N	0.518935454	None	None	N
N/E	0.6613	likely_pathogenic	0.5987	pathogenic	-0.399	Destabilizing	0.995	D	0.587	neutral	None	None	None	None	N
N/F	0.8402	likely_pathogenic	0.7952	pathogenic	-0.579	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
N/G	0.3234	likely_benign	0.3304	benign	-1.332	Destabilizing	0.998	D	0.551	neutral	None	None	None	None	N
N/H	0.151	likely_benign	0.1446	benign	-0.886	Destabilizing	0.608	D	0.294	neutral	N	0.518422254	None	None	N
N/I	0.7826	likely_pathogenic	0.6705	pathogenic	0.064	Stabilizing	0.999	D	0.797	deleterious	D	0.530032049	None	None	N
N/K	0.4589	ambiguous	0.4289	ambiguous	-0.135	Destabilizing	0.998	D	0.593	neutral	N	0.516241865	None	None	N
N/L	0.6173	likely_pathogenic	0.5416	ambiguous	0.064	Stabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
N/M	0.6877	likely_pathogenic	0.619	pathogenic	0.362	Stabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
N/P	0.9117	likely_pathogenic	0.8959	pathogenic	-0.242	Destabilizing	0.999	D	0.768	deleterious	None	None	None	None	N
N/Q	0.4859	ambiguous	0.4677	ambiguous	-0.726	Destabilizing	1.0	D	0.663	neutral	None	None	None	None	N
N/R	0.4476	ambiguous	0.4221	ambiguous	-0.245	Destabilizing	1.0	D	0.617	neutral	None	None	None	None	N
N/S	0.1203	likely_benign	0.1124	benign	-0.975	Destabilizing	0.645	D	0.316	neutral	N	0.482894853	None	None	N
N/T	0.3694	ambiguous	0.2961	benign	-0.603	Destabilizing	0.986	D	0.585	neutral	D	0.535502417	None	None	N
N/V	0.7567	likely_pathogenic	0.6491	pathogenic	-0.242	Destabilizing	0.994	D	0.777	deleterious	None	None	None	None	N
N/W	0.9156	likely_pathogenic	0.8976	pathogenic	-0.318	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
N/Y	0.3725	ambiguous	0.3169	benign	-0.08	Destabilizing	1.0	D	0.771	deleterious	N	0.518422254	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.