TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4931	15016;15017;15018	chr2:178735655;178735654;178735653	chr2:179600382;179600381;179600380
N2AB	4614	14065;14066;14067	chr2:178735655;178735654;178735653	chr2:179600382;179600381;179600380
N2A	3687	11284;11285;11286	chr2:178735655;178735654;178735653	chr2:179600382;179600381;179600380
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: G
• RefSeq wild type transcript codon: GGG
• RefSeq wild type template codon: CCC
• Domain: Ig-32
• Domain position: 44
• Structural Position: 73
• Q(SASA): 0.3423
• 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
G/R	rs767070682	-0.315	0.901	N	0.466	0.281	0.443695250439	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	9.3E-05	0	0
G/R	rs767070682	-0.315	0.901	N	0.466	0.281	0.443695250439	gnomAD-4.0.0	3.18289E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.7679E-05	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
G/A	0.149	likely_benign	0.1712	benign	-0.302	Destabilizing	0.349	N	0.445	neutral	N	0.509280938	None	None	N
G/C	0.269	likely_benign	0.3095	benign	-0.745	Destabilizing	0.996	D	0.581	neutral	None	None	None	None	N
G/D	0.361	ambiguous	0.4582	ambiguous	-0.732	Destabilizing	0.633	D	0.367	neutral	None	None	None	None	N
G/E	0.3145	likely_benign	0.3948	ambiguous	-0.847	Destabilizing	0.018	N	0.343	neutral	N	0.471064723	None	None	N
G/F	0.5979	likely_pathogenic	0.6788	pathogenic	-0.836	Destabilizing	0.987	D	0.557	neutral	None	None	None	None	N
G/H	0.4429	ambiguous	0.5371	ambiguous	-0.718	Destabilizing	0.989	D	0.482	neutral	None	None	None	None	N
G/I	0.3689	ambiguous	0.4524	ambiguous	-0.236	Destabilizing	0.923	D	0.559	neutral	None	None	None	None	N
G/K	0.4721	ambiguous	0.5622	ambiguous	-1.036	Destabilizing	0.633	D	0.429	neutral	None	None	None	None	N
G/L	0.396	ambiguous	0.4746	ambiguous	-0.236	Destabilizing	0.923	D	0.527	neutral	None	None	None	None	N
G/M	0.4814	ambiguous	0.5581	ambiguous	-0.387	Destabilizing	0.996	D	0.561	neutral	None	None	None	None	N
G/N	0.3142	likely_benign	0.3904	ambiguous	-0.632	Destabilizing	0.775	D	0.397	neutral	None	None	None	None	N
G/P	0.8765	likely_pathogenic	0.9078	pathogenic	-0.221	Destabilizing	0.961	D	0.465	neutral	None	None	None	None	N
G/Q	0.3367	likely_benign	0.4053	ambiguous	-0.846	Destabilizing	0.858	D	0.466	neutral	None	None	None	None	N
G/R	0.3227	likely_benign	0.3906	ambiguous	-0.644	Destabilizing	0.901	D	0.466	neutral	N	0.519955754	None	None	N
G/S	0.0961	likely_benign	0.1065	benign	-0.775	Destabilizing	0.118	N	0.241	neutral	None	None	None	None	N
G/T	0.1731	likely_benign	0.2168	benign	-0.816	Destabilizing	0.044	N	0.34	neutral	None	None	None	None	N
G/V	0.2307	likely_benign	0.2862	benign	-0.221	Destabilizing	0.901	D	0.525	neutral	D	0.59778955	None	None	N
G/W	0.4633	ambiguous	0.5336	ambiguous	-1.108	Destabilizing	0.995	D	0.573	neutral	D	0.659232842	None	None	N
G/Y	0.4998	ambiguous	0.5881	pathogenic	-0.723	Destabilizing	0.987	D	0.559	neutral	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.