TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34190	102793;102794;102795	chr2:178534047;178534046;178534045	chr2:179398774;179398773;179398772
N2AB	32549	97870;97871;97872	chr2:178534047;178534046;178534045	chr2:179398774;179398773;179398772
N2A	31622	95089;95090;95091	chr2:178534047;178534046;178534045	chr2:179398774;179398773;179398772
N2B	25125	75598;75599;75600	chr2:178534047;178534046;178534045	chr2:179398774;179398773;179398772
Novex-1	25250	75973;75974;75975	chr2:178534047;178534046;178534045	chr2:179398774;179398773;179398772
Novex-2	25317	76174;76175;76176	chr2:178534047;178534046;178534045	chr2:179398774;179398773;179398772
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Ig-160
• Domain position: 54
• Structural Position: 134
• Q(SASA): 0.0892
• 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/E	rs1690354224	None	1.0	N	0.815	0.564	0.735684033563	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
G/E	rs1690354224	None	1.0	N	0.815	0.564	0.735684033563	gnomAD-4.0.0	3.84243E-06	None	None	None	None	N	None	0	3.38926E-05	None	0	0	None	0	0	0	0	2.84349E-05

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	0.5143	ambiguous	0.5355	ambiguous	-0.296	Destabilizing	1.0	D	0.691	prob.neutral	N	0.501568539	None	None	N
G/C	0.6739	likely_pathogenic	0.726	pathogenic	-0.386	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
G/D	0.5569	ambiguous	0.6162	pathogenic	-0.838	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
G/E	0.6154	likely_pathogenic	0.6745	pathogenic	-0.8	Destabilizing	1.0	D	0.815	deleterious	N	0.520628965	None	None	N
G/F	0.9654	likely_pathogenic	0.972	pathogenic	-0.516	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
G/H	0.7717	likely_pathogenic	0.8065	pathogenic	-1.25	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
G/I	0.9422	likely_pathogenic	0.9512	pathogenic	0.364	Stabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
G/K	0.7305	likely_pathogenic	0.7572	pathogenic	-0.831	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
G/L	0.9459	likely_pathogenic	0.9532	pathogenic	0.364	Stabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
G/M	0.93	likely_pathogenic	0.9398	pathogenic	0.265	Stabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
G/N	0.5982	likely_pathogenic	0.6401	pathogenic	-0.681	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
G/P	0.9931	likely_pathogenic	0.9947	pathogenic	0.189	Stabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
G/Q	0.6835	likely_pathogenic	0.7279	pathogenic	-0.673	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
G/R	0.6036	likely_pathogenic	0.642	pathogenic	-0.804	Destabilizing	1.0	D	0.801	deleterious	N	0.499077005	None	None	N
G/S	0.2723	likely_benign	0.2972	benign	-0.978	Destabilizing	1.0	D	0.758	deleterious	None	None	None	None	N
G/T	0.724	likely_pathogenic	0.7489	pathogenic	-0.837	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
G/V	0.8926	likely_pathogenic	0.9109	pathogenic	0.189	Stabilizing	1.0	D	0.801	deleterious	N	0.510940289	None	None	N
G/W	0.9239	likely_pathogenic	0.9407	pathogenic	-1.148	Destabilizing	1.0	D	0.76	deleterious	None	None	None	None	N
G/Y	0.9042	likely_pathogenic	0.9201	pathogenic	-0.547	Destabilizing	1.0	D	0.775	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.