TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4832	14719;14720;14721	chr2:178735952;178735951;178735950	chr2:179600679;179600678;179600677
N2AB	4515	13768;13769;13770	chr2:178735952;178735951;178735950	chr2:179600679;179600678;179600677
N2A	3588	10987;10988;10989	chr2:178735952;178735951;178735950	chr2:179600679;179600678;179600677
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: GGT
• RefSeq wild type template codon: CCA
• Domain: Ig-31
• Domain position: 38
• Structural Position: 52
• Q(SASA): 0.359
• 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/D	rs1485727928	-0.83	0.995	N	0.668	0.424	0.252681307341	gnomAD-2.1.1	1.07E-05	None	None	None	None	N	None	0	0	None	0	1.53925E-04	None	0	None	0	0	0
G/D	rs1485727928	-0.83	0.995	N	0.668	0.424	0.252681307341	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	1.92753E-04	None	0	0	0	0	0
G/D	rs1485727928	-0.83	0.995	N	0.668	0.424	0.252681307341	gnomAD-4.0.0	5.12409E-06	None	None	None	None	N	None	0	0	None	0	7.27484E-05	None	0	0	0	0	2.84382E-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	0.2146	likely_benign	0.1504	benign	-0.255	Destabilizing	0.996	D	0.509	neutral	D	0.562608104	None	None	N
G/C	0.3337	likely_benign	0.2594	benign	-0.898	Destabilizing	1.0	D	0.697	prob.neutral	D	0.717100599	None	None	N
G/D	0.2416	likely_benign	0.2799	benign	-0.699	Destabilizing	0.995	D	0.668	neutral	N	0.472046325	None	None	N
G/E	0.2622	likely_benign	0.1976	benign	-0.872	Destabilizing	0.998	D	0.649	neutral	None	None	None	None	N
G/F	0.6946	likely_pathogenic	0.5384	ambiguous	-1.087	Destabilizing	1.0	D	0.712	prob.delet.	None	None	None	None	N
G/H	0.4306	ambiguous	0.3079	benign	-0.375	Destabilizing	1.0	D	0.673	neutral	None	None	None	None	N
G/I	0.4948	ambiguous	0.3385	benign	-0.528	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
G/K	0.4164	ambiguous	0.3096	benign	-0.649	Destabilizing	0.998	D	0.653	neutral	None	None	None	None	N
G/L	0.6029	likely_pathogenic	0.438	ambiguous	-0.528	Destabilizing	0.999	D	0.665	neutral	None	None	None	None	N
G/M	0.6047	likely_pathogenic	0.4518	ambiguous	-0.528	Destabilizing	1.0	D	0.7	prob.neutral	None	None	None	None	N
G/N	0.2826	likely_benign	0.1849	benign	-0.357	Destabilizing	0.683	D	0.372	neutral	None	None	None	None	N
G/P	0.9526	likely_pathogenic	0.8979	pathogenic	-0.41	Destabilizing	1.0	D	0.654	neutral	None	None	None	None	N
G/Q	0.3542	ambiguous	0.2629	benign	-0.672	Destabilizing	0.999	D	0.659	neutral	None	None	None	None	N
G/R	0.2586	likely_benign	0.2018	benign	-0.182	Destabilizing	0.999	D	0.628	neutral	D	0.599530278	None	None	N
G/S	0.1242	likely_benign	0.0934	benign	-0.462	Destabilizing	0.992	D	0.515	neutral	D	0.52448447	None	None	N
G/T	0.2714	likely_benign	0.1832	benign	-0.576	Destabilizing	0.998	D	0.639	neutral	None	None	None	None	N
G/V	0.3893	ambiguous	0.2667	benign	-0.41	Destabilizing	1.0	D	0.669	neutral	D	0.717100599	None	None	N
G/W	0.54	ambiguous	0.4264	ambiguous	-1.183	Destabilizing	1.0	D	0.661	neutral	None	None	None	None	N
G/Y	0.5298	ambiguous	0.3897	ambiguous	-0.86	Destabilizing	1.0	D	0.713	prob.delet.	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.