TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6518	19777;19778;19779	chr2:178728272;178728271;178728270	chr2:179592999;179592998;179592997
N2AB	6201	18826;18827;18828	chr2:178728272;178728271;178728270	chr2:179592999;179592998;179592997
N2A	5274	16045;16046;16047	chr2:178728272;178728271;178728270	chr2:179592999;179592998;179592997
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: GGA
• RefSeq wild type template codon: CCT
• Domain: Ig-49
• Domain position: 38
• Structural Position: 52
• Q(SASA): 0.3344
• 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	None	None	0.928	N	0.547	0.447	0.546952355657	gnomAD-4.0.0	1.59247E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86017E-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
G/A	0.3764	ambiguous	0.4167	ambiguous	-0.333	Destabilizing	0.273	N	0.384	neutral	N	0.503485463	None	None	N
G/C	0.4895	ambiguous	0.5244	ambiguous	-0.927	Destabilizing	0.038	N	0.445	neutral	None	None	None	None	N
G/D	0.1862	likely_benign	0.2465	benign	-0.426	Destabilizing	0.894	D	0.482	neutral	None	None	None	None	N
G/E	0.2525	likely_benign	0.3044	benign	-0.562	Destabilizing	0.864	D	0.547	neutral	N	0.492734588	None	None	N
G/F	0.8578	likely_pathogenic	0.87	pathogenic	-0.911	Destabilizing	0.894	D	0.637	neutral	None	None	None	None	N
G/H	0.5069	ambiguous	0.5669	pathogenic	-0.49	Destabilizing	0.995	D	0.558	neutral	None	None	None	None	N
G/I	0.7636	likely_pathogenic	0.7957	pathogenic	-0.388	Destabilizing	0.593	D	0.629	neutral	None	None	None	None	N
G/K	0.4449	ambiguous	0.5006	ambiguous	-0.844	Destabilizing	0.894	D	0.543	neutral	None	None	None	None	N
G/L	0.7943	likely_pathogenic	0.8188	pathogenic	-0.388	Destabilizing	0.809	D	0.603	neutral	None	None	None	None	N
G/M	0.7806	likely_pathogenic	0.8028	pathogenic	-0.556	Destabilizing	0.985	D	0.631	neutral	None	None	None	None	N
G/N	0.2701	likely_benign	0.3071	benign	-0.564	Destabilizing	0.894	D	0.465	neutral	None	None	None	None	N
G/P	0.9873	likely_pathogenic	0.9888	pathogenic	-0.335	Destabilizing	0.945	D	0.539	neutral	None	None	None	None	N
G/Q	0.3271	likely_benign	0.3825	ambiguous	-0.79	Destabilizing	0.945	D	0.545	neutral	None	None	None	None	N
G/R	0.3057	likely_benign	0.3528	ambiguous	-0.419	Destabilizing	0.928	D	0.547	neutral	N	0.509157003	None	None	N
G/S	0.1432	likely_benign	0.1564	benign	-0.754	Destabilizing	0.178	N	0.304	neutral	None	None	None	None	N
G/T	0.4414	ambiguous	0.4945	ambiguous	-0.808	Destabilizing	0.809	D	0.493	neutral	None	None	None	None	N
G/V	0.6606	likely_pathogenic	0.71	pathogenic	-0.335	Destabilizing	0.013	N	0.407	neutral	D	0.542353773	None	None	N
G/W	0.6684	likely_pathogenic	0.7033	pathogenic	-1.09	Destabilizing	0.995	D	0.582	neutral	None	None	None	None	N
G/Y	0.7137	likely_pathogenic	0.7339	pathogenic	-0.736	Destabilizing	0.985	D	0.633	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.