TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16877	50854;50855;50856	chr2:178611600;178611599;178611598	chr2:179476327;179476326;179476325
N2AB	15236	45931;45932;45933	chr2:178611600;178611599;178611598	chr2:179476327;179476326;179476325
N2A	14309	43150;43151;43152	chr2:178611600;178611599;178611598	chr2:179476327;179476326;179476325
N2B	7812	23659;23660;23661	chr2:178611600;178611599;178611598	chr2:179476327;179476326;179476325
Novex-1	7937	24034;24035;24036	chr2:178611600;178611599;178611598	chr2:179476327;179476326;179476325
Novex-2	8004	24235;24236;24237	chr2:178611600;178611599;178611598	chr2:179476327;179476326;179476325
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-11
• Domain position: 26
• Structural Position: 28
• Q(SASA): 0.6735
• 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
E/G	None	None	0.801	N	0.43	0.239	0.44307954383	gnomAD-4.0.0	1.5929E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86125E-06	0	0
E/Q	rs566364225	0.378	0.136	N	0.205	0.155	0.245101548738	gnomAD-2.1.1	1.21E-05	None	None	None	None	I	None	0	0	None	0	0	None	9.81E-05	None	0	0	0
E/Q	rs566364225	0.378	0.136	N	0.205	0.155	0.245101548738	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	0	2.06868E-04	0
E/Q	rs566364225	0.378	0.136	N	0.205	0.155	0.245101548738	1000 genomes	1.99681E-04	None	None	None	None	I	None	0	0	None	None	0	0	None	None	None	1E-03	None
E/Q	rs566364225	0.378	0.136	N	0.205	0.155	0.245101548738	gnomAD-4.0.0	5.12873E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	5.36193E-05	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
E/A	0.1811	likely_benign	0.1995	benign	-0.142	Destabilizing	0.625	D	0.381	neutral	N	0.465346757	None	None	I
E/C	0.9247	likely_pathogenic	0.9369	pathogenic	-0.25	Destabilizing	0.998	D	0.292	neutral	None	None	None	None	I
E/D	0.2039	likely_benign	0.2102	benign	-0.304	Destabilizing	0.012	N	0.193	neutral	N	0.475010338	None	None	I
E/F	0.8818	likely_pathogenic	0.9022	pathogenic	-0.051	Destabilizing	0.949	D	0.359	neutral	None	None	None	None	I
E/G	0.2251	likely_benign	0.2488	benign	-0.289	Destabilizing	0.801	D	0.43	neutral	N	0.483280564	None	None	I
E/H	0.6877	likely_pathogenic	0.6985	pathogenic	0.514	Stabilizing	0.974	D	0.355	neutral	None	None	None	None	I
E/I	0.465	ambiguous	0.499	ambiguous	0.196	Stabilizing	0.728	D	0.433	neutral	None	None	None	None	I
E/K	0.2285	likely_benign	0.2525	benign	0.377	Stabilizing	0.669	D	0.389	neutral	N	0.466053812	None	None	I
E/L	0.4335	ambiguous	0.4841	ambiguous	0.196	Stabilizing	0.007	N	0.209	neutral	None	None	None	None	I
E/M	0.5831	likely_pathogenic	0.6157	pathogenic	-0.005	Destabilizing	0.949	D	0.337	neutral	None	None	None	None	I
E/N	0.4138	ambiguous	0.455	ambiguous	0.022	Stabilizing	0.728	D	0.374	neutral	None	None	None	None	I
E/P	0.6317	likely_pathogenic	0.7141	pathogenic	0.102	Stabilizing	0.974	D	0.371	neutral	None	None	None	None	I
E/Q	0.1921	likely_benign	0.1876	benign	0.054	Stabilizing	0.136	N	0.205	neutral	N	0.472414888	None	None	I
E/R	0.388	ambiguous	0.4053	ambiguous	0.66	Stabilizing	0.842	D	0.385	neutral	None	None	None	None	I
E/S	0.2658	likely_benign	0.2934	benign	-0.11	Destabilizing	0.842	D	0.351	neutral	None	None	None	None	I
E/T	0.3362	likely_benign	0.3742	ambiguous	0.02	Stabilizing	0.842	D	0.428	neutral	None	None	None	None	I
E/V	0.2709	likely_benign	0.2885	benign	0.102	Stabilizing	0.051	N	0.231	neutral	N	0.484559149	None	None	I
E/W	0.9584	likely_pathogenic	0.9658	pathogenic	0.053	Stabilizing	0.998	D	0.321	neutral	None	None	None	None	I
E/Y	0.822	likely_pathogenic	0.8422	pathogenic	0.183	Stabilizing	0.974	D	0.367	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.