TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29789	89590;89591;89592	chr2:178553640;178553639;178553638	chr2:179418367;179418366;179418365
N2AB	28148	84667;84668;84669	chr2:178553640;178553639;178553638	chr2:179418367;179418366;179418365
N2A	27221	81886;81887;81888	chr2:178553640;178553639;178553638	chr2:179418367;179418366;179418365
N2B	20724	62395;62396;62397	chr2:178553640;178553639;178553638	chr2:179418367;179418366;179418365
Novex-1	20849	62770;62771;62772	chr2:178553640;178553639;178553638	chr2:179418367;179418366;179418365
Novex-2	20916	62971;62972;62973	chr2:178553640;178553639;178553638	chr2:179418367;179418366;179418365
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-105
• Domain position: 56
• Structural Position: 75
• Q(SASA): 0.494
• 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
E/D	None	None	0.822	N	0.421	0.145	0.0920862733494	gnomAD-4.0.0	6.84189E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99447E-07	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
E/A	0.1631	likely_benign	0.1483	benign	-0.6	Destabilizing	0.698	D	0.476	neutral	N	0.439615373	None	None	N
E/C	0.8164	likely_pathogenic	0.8152	pathogenic	-0.254	Destabilizing	0.998	D	0.631	neutral	None	None	None	None	N
E/D	0.158	likely_benign	0.1375	benign	-0.462	Destabilizing	0.822	D	0.421	neutral	N	0.441884887	None	None	N
E/F	0.6893	likely_pathogenic	0.6872	pathogenic	-0.216	Destabilizing	0.993	D	0.584	neutral	None	None	None	None	N
E/G	0.2084	likely_benign	0.1888	benign	-0.833	Destabilizing	0.822	D	0.454	neutral	N	0.438153936	None	None	N
E/H	0.488	ambiguous	0.4524	ambiguous	0.026	Stabilizing	0.978	D	0.465	neutral	None	None	None	None	N
E/I	0.2956	likely_benign	0.2926	benign	-0.003	Destabilizing	0.978	D	0.586	neutral	None	None	None	None	N
E/K	0.1882	likely_benign	0.1638	benign	0.189	Stabilizing	0.014	N	0.231	neutral	N	0.445791984	None	None	N
E/L	0.3551	ambiguous	0.353	ambiguous	-0.003	Destabilizing	0.956	D	0.495	neutral	None	None	None	None	N
E/M	0.3918	ambiguous	0.3812	ambiguous	0.123	Stabilizing	0.998	D	0.555	neutral	None	None	None	None	N
E/N	0.266	likely_benign	0.2367	benign	-0.354	Destabilizing	0.956	D	0.424	neutral	None	None	None	None	N
E/P	0.6001	likely_pathogenic	0.647	pathogenic	-0.182	Destabilizing	0.978	D	0.52	neutral	None	None	None	None	N
E/Q	0.1503	likely_benign	0.1428	benign	-0.263	Destabilizing	0.153	N	0.151	neutral	N	0.463510953	None	None	N
E/R	0.3051	likely_benign	0.2846	benign	0.469	Stabilizing	0.754	D	0.441	neutral	None	None	None	None	N
E/S	0.2208	likely_benign	0.1999	benign	-0.494	Destabilizing	0.86	D	0.434	neutral	None	None	None	None	N
E/T	0.2037	likely_benign	0.1917	benign	-0.284	Destabilizing	0.956	D	0.467	neutral	None	None	None	None	N
E/V	0.1864	likely_benign	0.1812	benign	-0.182	Destabilizing	0.942	D	0.482	neutral	N	0.451197804	None	None	N
E/W	0.8916	likely_pathogenic	0.8834	pathogenic	0.046	Stabilizing	0.998	D	0.637	neutral	None	None	None	None	N
E/Y	0.5897	likely_pathogenic	0.5798	pathogenic	0.051	Stabilizing	0.993	D	0.558	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.