TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26561	79906;79907;79908	chr2:178566451;178566450;178566449	chr2:179431178;179431177;179431176
N2AB	24920	74983;74984;74985	chr2:178566451;178566450;178566449	chr2:179431178;179431177;179431176
N2A	23993	72202;72203;72204	chr2:178566451;178566450;178566449	chr2:179431178;179431177;179431176
N2B	17496	52711;52712;52713	chr2:178566451;178566450;178566449	chr2:179431178;179431177;179431176
Novex-1	17621	53086;53087;53088	chr2:178566451;178566450;178566449	chr2:179431178;179431177;179431176
Novex-2	17688	53287;53288;53289	chr2:178566451;178566450;178566449	chr2:179431178;179431177;179431176
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Fn3-81
• Domain position: 75
• Structural Position: 106
• Q(SASA): 0.1236
• 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
I/L	rs777951468	-0.342	None	N	0.173	0.096	0.300784259202	gnomAD-2.1.1	2.01E-05	None	None	None	None	N	None	0	0	None	0	0	None	1.63409E-04	None	0	0	0
I/L	rs777951468	-0.342	None	N	0.173	0.096	0.300784259202	gnomAD-4.0.0	5.4748E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	8.11557E-05	1.65689E-05
I/M	rs558767363	-0.766	0.171	N	0.617	0.175	0.380223377699	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	5.57E-05	None	0	None	0	0	0
I/M	rs558767363	-0.766	0.171	N	0.617	0.175	0.380223377699	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	1.93498E-04	None	0	0	0	0	0
I/M	rs558767363	-0.766	0.171	N	0.617	0.175	0.380223377699	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	0	None	None	1E-03	0	None	None	None	0	None
I/M	rs558767363	-0.766	0.171	N	0.617	0.175	0.380223377699	gnomAD-4.0.0	2.02981E-06	None	None	None	None	N	None	0	0	None	0	1.13817E-04	None	0	0	1.205E-06	0	0
I/T	rs754674270	-2.613	0.012	N	0.646	0.357	0.585443171169	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
I/T	rs754674270	-2.613	0.012	N	0.646	0.357	0.585443171169	gnomAD-4.0.0	1.59196E-06	None	None	None	None	N	None	5.65867E-05	0	None	0	0	None	0	0	0	0	0
I/V	rs777951468	-0.974	None	N	0.146	0.077	0.346544149963	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
I/V	rs777951468	-0.974	None	N	0.146	0.077	0.346544149963	gnomAD-4.0.0	6.8435E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99525E-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
I/A	0.798	likely_pathogenic	0.7698	pathogenic	-2.149	Highly Destabilizing	0.016	N	0.655	neutral	None	None	None	None	N
I/C	0.8243	likely_pathogenic	0.8281	pathogenic	-1.321	Destabilizing	0.356	N	0.752	deleterious	None	None	None	None	N
I/D	0.9964	likely_pathogenic	0.9964	pathogenic	-2.652	Highly Destabilizing	0.356	N	0.813	deleterious	None	None	None	None	N
I/E	0.9917	likely_pathogenic	0.9919	pathogenic	-2.34	Highly Destabilizing	0.136	N	0.804	deleterious	None	None	None	None	N
I/F	0.1894	likely_benign	0.1957	benign	-1.273	Destabilizing	None	N	0.349	neutral	None	None	None	None	N
I/G	0.9453	likely_pathogenic	0.9446	pathogenic	-2.752	Highly Destabilizing	0.136	N	0.774	deleterious	None	None	None	None	N
I/H	0.9794	likely_pathogenic	0.9819	pathogenic	-2.481	Highly Destabilizing	0.864	D	0.842	deleterious	None	None	None	None	N
I/K	0.9845	likely_pathogenic	0.9866	pathogenic	-1.611	Destabilizing	0.106	N	0.79	deleterious	N	0.489187232	None	None	N
I/L	0.0953	likely_benign	0.0836	benign	-0.363	Destabilizing	None	N	0.173	neutral	N	0.46778341	None	None	N
I/M	0.1361	likely_benign	0.1315	benign	-0.387	Destabilizing	0.171	N	0.617	neutral	N	0.514558636	None	None	N
I/N	0.9516	likely_pathogenic	0.9557	pathogenic	-2.286	Highly Destabilizing	0.628	D	0.837	deleterious	None	None	None	None	N
I/P	0.9855	likely_pathogenic	0.9837	pathogenic	-0.945	Destabilizing	0.628	D	0.826	deleterious	None	None	None	None	N
I/Q	0.9815	likely_pathogenic	0.9827	pathogenic	-1.921	Destabilizing	0.628	D	0.839	deleterious	None	None	None	None	N
I/R	0.9723	likely_pathogenic	0.9755	pathogenic	-1.762	Destabilizing	0.295	N	0.839	deleterious	N	0.489187232	None	None	N
I/S	0.925	likely_pathogenic	0.9209	pathogenic	-2.89	Highly Destabilizing	0.072	N	0.742	deleterious	None	None	None	None	N
I/T	0.8769	likely_pathogenic	0.8669	pathogenic	-2.402	Highly Destabilizing	0.012	N	0.646	neutral	N	0.488680253	None	None	N
I/V	0.1044	likely_benign	0.0985	benign	-0.945	Destabilizing	None	N	0.146	neutral	N	0.417351802	None	None	N
I/W	0.941	likely_pathogenic	0.949	pathogenic	-1.693	Destabilizing	0.864	D	0.837	deleterious	None	None	None	None	N
I/Y	0.7794	likely_pathogenic	0.8055	pathogenic	-1.35	Destabilizing	0.038	N	0.701	prob.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.