TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5793	17602;17603;17604	chr2:178731389;178731388;178731387	chr2:179596116;179596115;179596114
N2AB	5476	16651;16652;16653	chr2:178731389;178731388;178731387	chr2:179596116;179596115;179596114
N2A	4549	13870;13871;13872	chr2:178731389;178731388;178731387	chr2:179596116;179596115;179596114
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-41
• Domain position: 64
• Structural Position: 145
• Q(SASA): 0.3173
• 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
E/K	rs1287275902	-0.403	0.006	N	0.165	0.235	0.263140351381	gnomAD-2.1.1	8.04E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	8.88E-06	0
E/K	rs1287275902	-0.403	0.006	N	0.165	0.235	0.263140351381	gnomAD-4.0.0	1.09472E-05	None	None	None	None	N	None	2.98829E-05	0	None	0	0	None	0	0	1.3492E-05	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
E/A	0.1847	likely_benign	0.1778	benign	-0.651	Destabilizing	0.01	N	0.153	neutral	N	0.470029573	None	None	N
E/C	0.9103	likely_pathogenic	0.8847	pathogenic	-0.423	Destabilizing	0.995	D	0.459	neutral	None	None	None	None	N
E/D	0.1442	likely_benign	0.1554	benign	-0.908	Destabilizing	0.425	N	0.261	neutral	N	0.458620501	None	None	N
E/F	0.8222	likely_pathogenic	0.8048	pathogenic	-0.084	Destabilizing	0.981	D	0.483	neutral	None	None	None	None	N
E/G	0.2022	likely_benign	0.2053	benign	-0.981	Destabilizing	0.425	N	0.414	neutral	N	0.492175714	None	None	N
E/H	0.4922	ambiguous	0.4908	ambiguous	-0.174	Destabilizing	0.944	D	0.385	neutral	None	None	None	None	N
E/I	0.5464	ambiguous	0.5136	ambiguous	0.238	Stabilizing	0.893	D	0.476	neutral	None	None	None	None	N
E/K	0.1829	likely_benign	0.1851	benign	-0.437	Destabilizing	0.006	N	0.165	neutral	N	0.474203242	None	None	N
E/L	0.4647	ambiguous	0.4524	ambiguous	0.238	Stabilizing	0.704	D	0.435	neutral	None	None	None	None	N
E/M	0.5152	ambiguous	0.4997	ambiguous	0.461	Stabilizing	0.981	D	0.447	neutral	None	None	None	None	N
E/N	0.2579	likely_benign	0.2707	benign	-0.89	Destabilizing	0.704	D	0.217	neutral	None	None	None	None	N
E/P	0.9037	likely_pathogenic	0.8991	pathogenic	-0.037	Destabilizing	0.828	D	0.405	neutral	None	None	None	None	N
E/Q	0.1483	likely_benign	0.1519	benign	-0.764	Destabilizing	0.065	N	0.116	neutral	N	0.438455872	None	None	N
E/R	0.3034	likely_benign	0.2963	benign	-0.077	Destabilizing	0.543	D	0.221	neutral	None	None	None	None	N
E/S	0.2062	likely_benign	0.2071	benign	-1.138	Destabilizing	0.085	N	0.137	neutral	None	None	None	None	N
E/T	0.2379	likely_benign	0.225	benign	-0.868	Destabilizing	0.031	N	0.181	neutral	None	None	None	None	N
E/V	0.3057	likely_benign	0.2852	benign	-0.037	Destabilizing	0.642	D	0.425	neutral	N	0.49252243	None	None	N
E/W	0.9319	likely_pathogenic	0.9259	pathogenic	0.16	Stabilizing	0.995	D	0.502	neutral	None	None	None	None	N
E/Y	0.7244	likely_pathogenic	0.7194	pathogenic	0.159	Stabilizing	0.981	D	0.471	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.