TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20495	61708;61709;61710	chr2:178590242;178590241;178590240	chr2:179454969;179454968;179454967
N2AB	18854	56785;56786;56787	chr2:178590242;178590241;178590240	chr2:179454969;179454968;179454967
N2A	17927	54004;54005;54006	chr2:178590242;178590241;178590240	chr2:179454969;179454968;179454967
N2B	11430	34513;34514;34515	chr2:178590242;178590241;178590240	chr2:179454969;179454968;179454967
Novex-1	11555	34888;34889;34890	chr2:178590242;178590241;178590240	chr2:179454969;179454968;179454967
Novex-2	11622	35089;35090;35091	chr2:178590242;178590241;178590240	chr2:179454969;179454968;179454967
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGC
• RefSeq wild type template codon: GCG
• Domain: Ig-121
• Domain position: 17
• Structural Position: 29
• Q(SASA): 0.516
• 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
R/C	rs370128504	-0.508	0.964	N	0.525	0.389	None	gnomAD-2.1.1	1.77E-05	None	None	None	None	N	None	0	0	None	0	0	None	4.07E-05	None	0	1.92E-05	1.8622E-04
R/C	rs370128504	-0.508	0.964	N	0.525	0.389	None	gnomAD-3.1.2	2.63E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	4.41E-05	2.07727E-04	0
R/C	rs370128504	-0.508	0.964	N	0.525	0.389	None	gnomAD-4.0.0	2.5809E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.74081E-05	8.15756E-05	3.25924E-05
R/G	rs370128504	-0.82	0.058	N	0.501	0.38	0.370240404367	gnomAD-2.1.1	3.09E-05	None	None	None	None	N	None	0	2.18259E-04	None	0	0	None	0	None	0	0	0
R/G	rs370128504	-0.82	0.058	N	0.501	0.38	0.370240404367	gnomAD-4.0.0	5.56867E-06	None	None	None	None	N	None	0	1.64923E-04	None	0	0	None	0	0	9.0944E-07	0	0
R/H	rs775137607	-1.116	None	N	0.31	0.114	None	gnomAD-2.1.1	5.81E-05	None	None	None	None	N	None	1.25429E-04	0	None	0	0	None	0	None	0	1.00284E-04	0
R/H	rs775137607	-1.116	None	N	0.31	0.114	None	gnomAD-3.1.2	1.11849E-04	None	None	None	None	N	None	1.44872E-04	0	0	0	0	None	0	0	1.47158E-04	2.07039E-04	0
R/H	rs775137607	-1.116	None	N	0.31	0.114	None	gnomAD-4.0.0	5.16057E-05	None	None	None	None	N	None	1.21336E-04	0	None	0	0	None	0	1.68407E-04	5.82365E-05	1.16293E-05	4.88743E-05
R/L	rs775137607	0.295	0.13	N	0.523	0.166	0.273938319068	gnomAD-2.1.1	8.82E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.92E-05	0
R/L	rs775137607	0.295	0.13	N	0.523	0.166	0.273938319068	gnomAD-4.0.0	2.78362E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.63737E-06	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
R/A	0.4157	ambiguous	0.4721	ambiguous	-0.439	Destabilizing	0.031	N	0.521	neutral	None	None	None	None	N
R/C	0.1694	likely_benign	0.1893	benign	-0.435	Destabilizing	0.964	D	0.525	neutral	N	0.477519352	None	None	N
R/D	0.661	likely_pathogenic	0.7114	pathogenic	-0.013	Destabilizing	0.038	N	0.517	neutral	None	None	None	None	N
R/E	0.4281	ambiguous	0.4678	ambiguous	0.082	Stabilizing	0.016	N	0.559	neutral	None	None	None	None	N
R/F	0.5567	ambiguous	0.6047	pathogenic	-0.439	Destabilizing	0.214	N	0.532	neutral	None	None	None	None	N
R/G	0.3363	likely_benign	0.4156	ambiguous	-0.706	Destabilizing	0.058	N	0.501	neutral	N	0.495370118	None	None	N
R/H	0.0935	likely_benign	0.0958	benign	-1.063	Destabilizing	None	N	0.31	neutral	N	0.452311526	None	None	N
R/I	0.3211	likely_benign	0.3682	ambiguous	0.255	Stabilizing	0.356	N	0.549	neutral	None	None	None	None	N
R/K	0.1119	likely_benign	0.1252	benign	-0.479	Destabilizing	None	N	0.307	neutral	None	None	None	None	N
R/L	0.2965	likely_benign	0.3242	benign	0.255	Stabilizing	0.13	N	0.523	neutral	N	0.483528361	None	None	N
R/M	0.3746	ambiguous	0.4065	ambiguous	-0.088	Destabilizing	0.628	D	0.549	neutral	None	None	None	None	N
R/N	0.4409	ambiguous	0.508	ambiguous	-0.016	Destabilizing	None	N	0.347	neutral	None	None	None	None	N
R/P	0.8213	likely_pathogenic	0.8531	pathogenic	0.045	Stabilizing	0.515	D	0.546	neutral	N	0.483849228	None	None	N
R/Q	0.1132	likely_benign	0.1204	benign	-0.19	Destabilizing	0.072	N	0.523	neutral	None	None	None	None	N
R/S	0.4246	ambiguous	0.4745	ambiguous	-0.64	Destabilizing	0.058	N	0.526	neutral	N	0.475428953	None	None	N
R/T	0.2338	likely_benign	0.2674	benign	-0.381	Destabilizing	0.072	N	0.532	neutral	None	None	None	None	N
R/V	0.3456	ambiguous	0.3999	ambiguous	0.045	Stabilizing	0.136	N	0.535	neutral	None	None	None	None	N
R/W	0.2427	likely_benign	0.2539	benign	-0.241	Destabilizing	0.864	D	0.551	neutral	None	None	None	None	N
R/Y	0.3979	ambiguous	0.4351	ambiguous	0.097	Stabilizing	0.12	N	0.543	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.