TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25683	77272;77273;77274	chr2:178569085;178569084;178569083	chr2:179433812;179433811;179433810
N2AB	24042	72349;72350;72351	chr2:178569085;178569084;178569083	chr2:179433812;179433811;179433810
N2A	23115	69568;69569;69570	chr2:178569085;178569084;178569083	chr2:179433812;179433811;179433810
N2B	16618	50077;50078;50079	chr2:178569085;178569084;178569083	chr2:179433812;179433811;179433810
Novex-1	16743	50452;50453;50454	chr2:178569085;178569084;178569083	chr2:179433812;179433811;179433810
Novex-2	16810	50653;50654;50655	chr2:178569085;178569084;178569083	chr2:179433812;179433811;179433810
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-74
• Domain position: 83
• Structural Position: 117
• Q(SASA): 0.3859
• Predicted PPI site: I

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/F	rs375611562	-1.308	0.073	N	0.583	0.215	0.424549175451	gnomAD-2.1.1	8.05E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
I/F	rs375611562	-1.308	0.073	N	0.583	0.215	0.424549175451	gnomAD-4.0.0	1.36873E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	1.73611E-04	0	0	1.65717E-05
I/M	rs755225678	-0.533	None	N	0.339	0.072	0.19670166235	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
I/M	rs755225678	-0.533	None	N	0.339	0.072	0.19670166235	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
I/M	rs755225678	-0.533	None	N	0.339	0.072	0.19670166235	gnomAD-4.0.0	4.06001E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	4.81989E-06	0	0
I/S	None	None	0.283	N	0.635	0.35	0.640388181781	gnomAD-4.0.0	1.59208E-06	None	None	None	None	I	None	0	0	None	0	2.77516E-05	None	0	0	0	0	0
I/T	rs1707153104	None	0.033	N	0.563	0.255	0.525049811399	gnomAD-4.0.0	1.59208E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85981E-06	0	0
I/V	rs375611562	-0.862	None	N	0.211	0.065	None	gnomAD-2.1.1	1.79E-05	None	None	None	None	I	None	2.0668E-04	0	None	0	0	None	0	None	0	0	0
I/V	rs375611562	-0.862	None	N	0.211	0.065	None	gnomAD-3.1.2	7.89E-05	None	None	None	None	I	None	2.65418E-04	0	0	0	0	None	0	0	1.47E-05	0	0
I/V	rs375611562	-0.862	None	N	0.211	0.065	None	gnomAD-4.0.0	1.17771E-05	None	None	None	None	I	None	2.40372E-04	0	None	0	0	None	0	0	8.47767E-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	0.2206	likely_benign	0.2273	benign	-1.015	Destabilizing	0.03	N	0.495	neutral	None	None	None	None	I
I/C	0.6199	likely_pathogenic	0.6483	pathogenic	-0.864	Destabilizing	0.924	D	0.59	neutral	None	None	None	None	I
I/D	0.8314	likely_pathogenic	0.8221	pathogenic	-0.269	Destabilizing	0.514	D	0.661	neutral	None	None	None	None	I
I/E	0.697	likely_pathogenic	0.6927	pathogenic	-0.341	Destabilizing	0.439	N	0.657	neutral	None	None	None	None	I
I/F	0.1832	likely_benign	0.2049	benign	-0.915	Destabilizing	0.073	N	0.583	neutral	N	0.494891089	None	None	I
I/G	0.6694	likely_pathogenic	0.6709	pathogenic	-1.213	Destabilizing	0.343	N	0.649	neutral	None	None	None	None	I
I/H	0.6241	likely_pathogenic	0.64	pathogenic	-0.377	Destabilizing	0.835	D	0.655	neutral	None	None	None	None	I
I/K	0.4978	ambiguous	0.4934	ambiguous	-0.454	Destabilizing	0.015	N	0.651	neutral	None	None	None	None	I
I/L	0.1281	likely_benign	0.1337	benign	-0.6	Destabilizing	None	N	0.195	neutral	N	0.508320523	None	None	I
I/M	0.1154	likely_benign	0.1234	benign	-0.509	Destabilizing	None	N	0.339	neutral	N	0.506917801	None	None	I
I/N	0.4411	ambiguous	0.4201	ambiguous	-0.29	Destabilizing	0.444	N	0.662	neutral	N	0.489749301	None	None	I
I/P	0.5135	ambiguous	0.5315	ambiguous	-0.704	Destabilizing	0.763	D	0.663	neutral	None	None	None	None	I
I/Q	0.5281	ambiguous	0.5425	ambiguous	-0.551	Destabilizing	0.178	N	0.665	neutral	None	None	None	None	I
I/R	0.3666	ambiguous	0.3705	ambiguous	0.142	Stabilizing	0.172	N	0.663	neutral	None	None	None	None	I
I/S	0.3253	likely_benign	0.3132	benign	-0.86	Destabilizing	0.283	N	0.635	neutral	N	0.518364159	None	None	I
I/T	0.1281	likely_benign	0.132	benign	-0.82	Destabilizing	0.033	N	0.563	neutral	N	0.508128522	None	None	I
I/V	0.0681	likely_benign	0.0663	benign	-0.704	Destabilizing	None	N	0.211	neutral	N	0.437556503	None	None	I
I/W	0.752	likely_pathogenic	0.7933	pathogenic	-0.86	Destabilizing	0.948	D	0.693	prob.neutral	None	None	None	None	I
I/Y	0.5825	likely_pathogenic	0.6073	pathogenic	-0.616	Destabilizing	0.047	N	0.609	neutral	None	None	None	None	I

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.