TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16509	49750;49751;49752	chr2:178613758;178613757;178613756	chr2:179478485;179478484;179478483
N2AB	14868	44827;44828;44829	chr2:178613758;178613757;178613756	chr2:179478485;179478484;179478483
N2A	13941	42046;42047;42048	chr2:178613758;178613757;178613756	chr2:179478485;179478484;179478483
N2B	7444	22555;22556;22557	chr2:178613758;178613757;178613756	chr2:179478485;179478484;179478483
Novex-1	7569	22930;22931;22932	chr2:178613758;178613757;178613756	chr2:179478485;179478484;179478483
Novex-2	7636	23131;23132;23133	chr2:178613758;178613757;178613756	chr2:179478485;179478484;179478483
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-7
• Domain position: 60
• Structural Position: 90
• Q(SASA): 0.4379
• 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/S	rs779933778	-0.92	0.826	N	0.401	0.169	0.202086224978	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	5.59E-05	None	0	None	0	0	0
T/S	rs779933778	-0.92	0.826	N	0.401	0.169	0.202086224978	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	1.94553E-04	None	0	0	0	0	0
T/S	rs779933778	-0.92	0.826	N	0.401	0.169	0.202086224978	gnomAD-4.0.0	6.57999E-06	None	None	None	None	N	None	0	0	None	0	1.94553E-04	None	0	0	0	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
T/A	0.1142	likely_benign	0.0961	benign	-1.044	Destabilizing	0.826	D	0.401	neutral	N	0.479885294	None	None	N
T/C	0.5703	likely_pathogenic	0.3878	ambiguous	-0.514	Destabilizing	0.999	D	0.535	neutral	None	None	None	None	N
T/D	0.716	likely_pathogenic	0.6384	pathogenic	-0.074	Destabilizing	0.884	D	0.398	neutral	None	None	None	None	N
T/E	0.572	likely_pathogenic	0.4941	ambiguous	-0.018	Destabilizing	0.939	D	0.414	neutral	None	None	None	None	N
T/F	0.47	ambiguous	0.3931	ambiguous	-1.037	Destabilizing	0.991	D	0.575	neutral	None	None	None	None	N
T/G	0.4161	ambiguous	0.3159	benign	-1.352	Destabilizing	0.939	D	0.488	neutral	None	None	None	None	N
T/H	0.4202	ambiguous	0.3166	benign	-1.515	Destabilizing	0.991	D	0.565	neutral	None	None	None	None	N
T/I	0.2814	likely_benign	0.2239	benign	-0.295	Destabilizing	0.852	D	0.435	neutral	N	0.515352716	None	None	N
T/K	0.4221	ambiguous	0.3693	ambiguous	-0.559	Destabilizing	0.134	N	0.361	neutral	N	0.484846742	None	None	N
T/L	0.2041	likely_benign	0.1605	benign	-0.295	Destabilizing	0.759	D	0.415	neutral	None	None	None	None	N
T/M	0.1487	likely_benign	0.1217	benign	-0.096	Destabilizing	0.991	D	0.543	neutral	None	None	None	None	N
T/N	0.2151	likely_benign	0.1616	benign	-0.661	Destabilizing	0.079	N	0.225	neutral	None	None	None	None	N
T/P	0.7922	likely_pathogenic	0.7981	pathogenic	-0.512	Destabilizing	0.996	D	0.56	neutral	D	0.534280391	None	None	N
T/Q	0.3583	ambiguous	0.2777	benign	-0.689	Destabilizing	0.982	D	0.561	neutral	None	None	None	None	N
T/R	0.347	ambiguous	0.3302	benign	-0.456	Destabilizing	0.852	D	0.467	neutral	N	0.473464937	None	None	N
T/S	0.1498	likely_benign	0.1234	benign	-1.017	Destabilizing	0.826	D	0.401	neutral	N	0.433995298	None	None	N
T/V	0.1948	likely_benign	0.1478	benign	-0.512	Destabilizing	0.17	N	0.29	neutral	None	None	None	None	N
T/W	0.8486	likely_pathogenic	0.7812	pathogenic	-0.982	Destabilizing	0.999	D	0.614	neutral	None	None	None	None	N
T/Y	0.5256	ambiguous	0.4126	ambiguous	-0.725	Destabilizing	0.997	D	0.576	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.