TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2238	6937;6938;6939	chr2:178774999;178774998;178774997	chr2:179639726;179639725;179639724
N2AB	2238	6937;6938;6939	chr2:178774999;178774998;178774997	chr2:179639726;179639725;179639724
N2A	2238	6937;6938;6939	chr2:178774999;178774998;178774997	chr2:179639726;179639725;179639724
N2B	2192	6799;6800;6801	chr2:178774999;178774998;178774997	chr2:179639726;179639725;179639724
Novex-1	2192	6799;6800;6801	chr2:178774999;178774998;178774997	chr2:179639726;179639725;179639724
Novex-2	2192	6799;6800;6801	chr2:178774999;178774998;178774997	chr2:179639726;179639725;179639724
Novex-3	2238	6937;6938;6939	chr2:178774999;178774998;178774997	chr2:179639726;179639725;179639724

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACG
• RefSeq wild type template codon: TGC
• Domain: Ig-11
• Domain position: 65
• Structural Position: 146
• Q(SASA): 0.7146
• 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
T/A	rs747377115	0.153	None	N	0.055	0.055	0.0138822411134	gnomAD-2.1.1	3.98E-06	None	None	None	None	N	None	0	0	None	0	5.45E-05	None	0	None	0	0	0
T/A	rs747377115	0.153	None	N	0.055	0.055	0.0138822411134	gnomAD-4.0.0	6.84129E-07	None	None	None	None	N	None	0	0	None	0	2.52131E-05	None	0	0	0	0	0
T/K	None	None	None	N	0.141	0.078	0.0297737177859	gnomAD-4.0.0	6.84146E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.9936E-07	0	0
T/M	rs201284459	0.279	0.002	N	0.094	0.077	None	gnomAD-2.1.1	1.62834E-04	None	None	None	None	N	None	8.01E-05	3.67252E-04	None	0	0	None	3.27E-05	None	0	2.09387E-04	4.1632E-04
T/M	rs201284459	0.279	0.002	N	0.094	0.077	None	gnomAD-3.1.2	5.26E-05	None	None	None	None	N	None	2.41E-05	1.96515E-04	0	0	0	None	0	0	5.88E-05	0	0
T/M	rs201284459	0.279	0.002	N	0.094	0.077	None	gnomAD-4.0.0	1.17733E-04	None	None	None	None	N	None	4.00438E-05	3.16772E-04	None	0	0	None	0	1.6442E-03	1.17804E-04	7.68572E-05	1.92074E-04
T/P	rs747377115	None	0.055	N	0.305	0.034	0.0297737177859	gnomAD-4.0.0	1.23143E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.61882E-05	0	0
T/R	rs201284459	0.409	0.07	N	0.338	0.064	0.0666544352282	gnomAD-2.1.1	2.39E-05	None	None	None	None	N	None	0	5.79E-05	None	0	0	None	1.30676E-04	None	0	0	0
T/R	rs201284459	0.409	0.07	N	0.338	0.064	0.0666544352282	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
T/R	rs201284459	0.409	0.07	N	0.338	0.064	0.0666544352282	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	1.4E-03	None	None	0	0	None	None	None	0	None
T/R	rs201284459	0.409	0.07	N	0.338	0.064	0.0666544352282	gnomAD-4.0.0	1.11528E-05	None	None	None	None	N	None	0	5E-05	None	0	2.22975E-05	None	0	0	0	1.53721E-04	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
T/A	0.0615	likely_benign	0.0607	benign	-0.28	Destabilizing	None	N	0.055	neutral	N	0.340617602	None	None	N
T/C	0.2824	likely_benign	0.2757	benign	-0.136	Destabilizing	0.356	N	0.245	neutral	None	None	None	None	N
T/D	0.1749	likely_benign	0.1786	benign	0.052	Stabilizing	0.038	N	0.336	neutral	None	None	None	None	N
T/E	0.1369	likely_benign	0.1378	benign	-0.035	Destabilizing	0.016	N	0.257	neutral	None	None	None	None	N
T/F	0.1126	likely_benign	0.1187	benign	-0.832	Destabilizing	0.072	N	0.41	neutral	None	None	None	None	N
T/G	0.133	likely_benign	0.1316	benign	-0.392	Destabilizing	0.016	N	0.229	neutral	None	None	None	None	N
T/H	0.128	likely_benign	0.1296	benign	-0.702	Destabilizing	0.356	N	0.319	neutral	None	None	None	None	N
T/I	0.0769	likely_benign	0.0732	benign	-0.106	Destabilizing	0.016	N	0.286	neutral	None	None	None	None	N
T/K	0.0761	likely_benign	0.0788	benign	-0.297	Destabilizing	None	N	0.141	neutral	N	0.331479027	None	None	N
T/L	0.0504	likely_benign	0.0542	benign	-0.106	Destabilizing	None	N	0.095	neutral	None	None	None	None	N
T/M	0.056	likely_benign	0.0582	benign	0.099	Stabilizing	0.002	N	0.094	neutral	N	0.310616629	None	None	N
T/N	0.0735	likely_benign	0.0769	benign	-0.011	Destabilizing	0.038	N	0.142	neutral	None	None	None	None	N
T/P	0.0768	likely_benign	0.0756	benign	-0.137	Destabilizing	0.055	N	0.305	neutral	N	0.319270946	None	None	N
T/Q	0.1146	likely_benign	0.1175	benign	-0.27	Destabilizing	0.072	N	0.319	neutral	None	None	None	None	N
T/R	0.0729	likely_benign	0.0775	benign	-0.011	Destabilizing	0.07	N	0.338	neutral	N	0.340838118	None	None	N
T/S	0.0766	likely_benign	0.0776	benign	-0.197	Destabilizing	None	N	0.086	neutral	N	0.341722604	None	None	N
T/V	0.0708	likely_benign	0.0697	benign	-0.137	Destabilizing	None	N	0.085	neutral	None	None	None	None	N
T/W	0.3534	ambiguous	0.3619	ambiguous	-0.859	Destabilizing	0.864	D	0.316	neutral	None	None	None	None	N
T/Y	0.1303	likely_benign	0.1342	benign	-0.562	Destabilizing	0.356	N	0.43	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.