TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25744	77455;77456;77457	chr2:178568902;178568901;178568900	chr2:179433629;179433628;179433627
N2AB	24103	72532;72533;72534	chr2:178568902;178568901;178568900	chr2:179433629;179433628;179433627
N2A	23176	69751;69752;69753	chr2:178568902;178568901;178568900	chr2:179433629;179433628;179433627
N2B	16679	50260;50261;50262	chr2:178568902;178568901;178568900	chr2:179433629;179433628;179433627
Novex-1	16804	50635;50636;50637	chr2:178568902;178568901;178568900	chr2:179433629;179433628;179433627
Novex-2	16871	50836;50837;50838	chr2:178568902;178568901;178568900	chr2:179433629;179433628;179433627
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-75
• Domain position: 47
• Structural Position: 64
• Q(SASA): 0.6327
• 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
K/N	rs1482499927	0.367	0.325	N	0.218	0.098	0.0884992946249	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	5.57E-05	None	0	None	0	0	0
K/N	rs1482499927	0.367	0.325	N	0.218	0.098	0.0884992946249	gnomAD-4.0.0	6.84423E-07	None	None	None	None	N	None	0	0	None	0	2.52067E-05	None	0	0	0	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
K/A	0.3016	likely_benign	0.3141	benign	0.055	Stabilizing	0.211	N	0.207	neutral	None	None	None	None	N
K/C	0.6661	likely_pathogenic	0.6893	pathogenic	-0.266	Destabilizing	1.0	D	0.291	neutral	None	None	None	None	N
K/D	0.4733	ambiguous	0.497	ambiguous	-0.071	Destabilizing	0.96	D	0.276	neutral	None	None	None	None	N
K/E	0.1875	likely_benign	0.2108	benign	-0.076	Destabilizing	0.915	D	0.289	neutral	N	0.457179627	None	None	N
K/F	0.7004	likely_pathogenic	0.717	pathogenic	-0.24	Destabilizing	0.998	D	0.291	neutral	None	None	None	None	N
K/G	0.4103	ambiguous	0.4337	ambiguous	-0.098	Destabilizing	0.951	D	0.281	neutral	None	None	None	None	N
K/H	0.2615	likely_benign	0.2717	benign	-0.246	Destabilizing	0.993	D	0.266	neutral	None	None	None	None	N
K/I	0.2565	likely_benign	0.2812	benign	0.375	Stabilizing	0.787	D	0.322	neutral	N	0.513363771	None	None	N
K/L	0.3183	likely_benign	0.3429	ambiguous	0.375	Stabilizing	0.583	D	0.304	neutral	None	None	None	None	N
K/M	0.1962	likely_benign	0.2111	benign	0.038	Stabilizing	0.992	D	0.269	neutral	None	None	None	None	N
K/N	0.2794	likely_benign	0.2922	benign	0.211	Stabilizing	0.325	N	0.218	neutral	N	0.479192482	None	None	N
K/P	0.792	likely_pathogenic	0.8013	pathogenic	0.294	Stabilizing	0.997	D	0.296	neutral	None	None	None	None	N
K/Q	0.1209	likely_benign	0.1294	benign	0.067	Stabilizing	0.969	D	0.277	neutral	N	0.465647181	None	None	N
K/R	0.0899	likely_benign	0.0912	benign	0.009	Stabilizing	0.931	D	0.265	neutral	N	0.453430033	None	None	N
K/S	0.3412	ambiguous	0.3621	ambiguous	-0.198	Destabilizing	0.908	D	0.311	neutral	None	None	None	None	N
K/T	0.1285	likely_benign	0.1356	benign	-0.073	Destabilizing	0.057	N	0.167	neutral	N	0.440674166	None	None	N
K/V	0.244	likely_benign	0.268	benign	0.294	Stabilizing	0.648	D	0.327	neutral	None	None	None	None	N
K/W	0.7724	likely_pathogenic	0.788	pathogenic	-0.325	Destabilizing	1.0	D	0.339	neutral	None	None	None	None	N
K/Y	0.5487	ambiguous	0.5743	pathogenic	0.035	Stabilizing	0.98	D	0.281	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.