TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31105	93538;93539;93540	chr2:178548313;178548312;178548311	chr2:179413040;179413039;179413038
N2AB	29464	88615;88616;88617	chr2:178548313;178548312;178548311	chr2:179413040;179413039;179413038
N2A	28537	85834;85835;85836	chr2:178548313;178548312;178548311	chr2:179413040;179413039;179413038
N2B	22040	66343;66344;66345	chr2:178548313;178548312;178548311	chr2:179413040;179413039;179413038
Novex-1	22165	66718;66719;66720	chr2:178548313;178548312;178548311	chr2:179413040;179413039;179413038
Novex-2	22232	66919;66920;66921	chr2:178548313;178548312;178548311	chr2:179413040;179413039;179413038
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-114
• Domain position: 90
• Structural Position: 124
• Q(SASA): 0.6928
• Predicted PPI site: I

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
P/T	None	None	0.01	N	0.201	0.098	0.191931220699	gnomAD-4.0.0	1.59118E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.02389E-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
P/A	0.0545	likely_benign	0.0678	benign	-0.731	Destabilizing	0.278	N	0.316	neutral	N	0.422178832	None	None	I
P/C	0.3171	likely_benign	0.4304	ambiguous	-0.497	Destabilizing	0.995	D	0.629	neutral	None	None	None	None	I
P/D	0.2583	likely_benign	0.2953	benign	-0.925	Destabilizing	0.712	D	0.465	neutral	None	None	None	None	I
P/E	0.1766	likely_benign	0.1976	benign	-0.968	Destabilizing	0.553	D	0.412	neutral	None	None	None	None	I
P/F	0.3246	likely_benign	0.4275	ambiguous	-0.759	Destabilizing	0.946	D	0.637	neutral	None	None	None	None	I
P/G	0.1691	likely_benign	0.2079	benign	-0.912	Destabilizing	0.712	D	0.438	neutral	None	None	None	None	I
P/H	0.1547	likely_benign	0.1936	benign	-0.369	Destabilizing	0.985	D	0.551	neutral	None	None	None	None	I
P/I	0.1672	likely_benign	0.2305	benign	-0.355	Destabilizing	0.897	D	0.676	prob.neutral	None	None	None	None	I
P/K	0.182	likely_benign	0.2118	benign	-0.615	Destabilizing	0.553	D	0.333	neutral	None	None	None	None	I
P/L	0.0791	likely_benign	0.0983	benign	-0.355	Destabilizing	0.483	N	0.503	neutral	N	0.487150243	None	None	I
P/M	0.1502	likely_benign	0.2007	benign	-0.527	Destabilizing	0.995	D	0.544	neutral	None	None	None	None	I
P/N	0.1633	likely_benign	0.2237	benign	-0.405	Destabilizing	0.897	D	0.565	neutral	None	None	None	None	I
P/Q	0.1113	likely_benign	0.135	benign	-0.603	Destabilizing	0.055	N	0.261	neutral	N	0.463639195	None	None	I
P/R	0.1531	likely_benign	0.1696	benign	-0.115	Destabilizing	0.766	D	0.56	neutral	N	0.467932551	None	None	I
P/S	0.0849	likely_benign	0.1074	benign	-0.694	Destabilizing	0.483	N	0.385	neutral	N	0.361957092	None	None	I
P/T	0.0661	likely_benign	0.0821	benign	-0.645	Destabilizing	0.01	N	0.201	neutral	N	0.39732046	None	None	I
P/V	0.115	likely_benign	0.1479	benign	-0.45	Destabilizing	0.553	D	0.435	neutral	None	None	None	None	I
P/W	0.4976	ambiguous	0.5769	pathogenic	-0.891	Destabilizing	0.995	D	0.687	prob.delet.	None	None	None	None	I
P/Y	0.3233	likely_benign	0.4084	ambiguous	-0.588	Destabilizing	0.982	D	0.632	neutral	None	None	None	None	I

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.