TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16151	48676;48677;48678	chr2:178615650;178615649;178615648	chr2:179480377;179480376;179480375
N2AB	14510	43753;43754;43755	chr2:178615650;178615649;178615648	chr2:179480377;179480376;179480375
N2A	13583	40972;40973;40974	chr2:178615650;178615649;178615648	chr2:179480377;179480376;179480375
N2B	7086	21481;21482;21483	chr2:178615650;178615649;178615648	chr2:179480377;179480376;179480375
Novex-1	7211	21856;21857;21858	chr2:178615650;178615649;178615648	chr2:179480377;179480376;179480375
Novex-2	7278	22057;22058;22059	chr2:178615650;178615649;178615648	chr2:179480377;179480376;179480375
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-4
• Domain position: 97
• Structural Position: 132
• Q(SASA): 1.1034
• 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/A	rs186497293	0.115	None	N	0.03	0.159	None	gnomAD-2.1.1	2.64832E-04	None	None	None	None	N	None	2.52588E-03	1.70116E-04	None	0	1.54242E-04	None	0	None	0	2.35E-05	1.40726E-04
T/A	rs186497293	0.115	None	N	0.03	0.159	None	gnomAD-3.1.2	6.71866E-04	None	None	None	None	N	None	2.27174E-03	3.94115E-04	0	0	1.95542E-04	None	0	0	1.47E-05	0	0
T/A	rs186497293	0.115	None	N	0.03	0.159	None	1000 genomes	1.19808E-03	None	None	None	None	N	None	3.8E-03	1.4E-03	None	None	0	0	None	None	None	0	None
T/A	rs186497293	0.115	None	N	0.03	0.159	None	gnomAD-4.0.0	1.32734E-04	None	None	None	None	N	None	2.33726E-03	2.50392E-04	None	0	6.70211E-05	None	0	0	8.48243E-06	0	1.76299E-04
T/N	rs1188604829	None	0.011	N	0.178	0.126	0.339793275041	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
T/N	rs1188604829	None	0.011	N	0.178	0.126	0.339793275041	gnomAD-4.0.0	6.58285E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47232E-05	0	0
T/P	rs186497293	0.035	0.026	N	0.339	0.089	0.348324211639	gnomAD-2.1.1	8.06E-06	None	None	None	None	N	None	6.48E-05	0	None	0	0	None	0	None	0	8.91E-06	0
T/P	rs186497293	0.035	0.026	N	0.339	0.089	0.348324211639	gnomAD-3.1.2	3.29E-05	None	None	None	None	N	None	9.67E-05	0	0	0	0	None	0	0	1.47E-05	0	0
T/P	rs186497293	0.035	0.026	N	0.339	0.089	0.348324211639	gnomAD-4.0.0	4.96239E-06	None	None	None	None	N	None	6.68878E-05	0	None	0	0	None	0	0	2.54471E-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
T/A	0.0536	likely_benign	0.0517	benign	-0.249	Destabilizing	None	N	0.03	neutral	N	0.503995291	None	None	N
T/C	0.2653	likely_benign	0.316	benign	-0.569	Destabilizing	0.204	N	0.231	neutral	None	None	None	None	N
T/D	0.297	likely_benign	0.2654	benign	-0.233	Destabilizing	0.015	N	0.229	neutral	None	None	None	None	N
T/E	0.2515	likely_benign	0.2278	benign	-0.324	Destabilizing	0.015	N	0.191	neutral	None	None	None	None	N
T/F	0.1573	likely_benign	0.1907	benign	-0.936	Destabilizing	0.035	N	0.395	neutral	None	None	None	None	N
T/G	0.151	likely_benign	0.1695	benign	-0.265	Destabilizing	0.003	N	0.189	neutral	None	None	None	None	N
T/H	0.2156	likely_benign	0.2302	benign	-0.356	Destabilizing	0.439	N	0.29	neutral	None	None	None	None	N
T/I	0.0868	likely_benign	0.1105	benign	-0.318	Destabilizing	None	N	0.087	neutral	D	0.551599501	None	None	N
T/K	0.2498	likely_benign	0.2319	benign	-0.436	Destabilizing	0.015	N	0.259	neutral	None	None	None	None	N
T/L	0.0653	likely_benign	0.0774	benign	-0.318	Destabilizing	0.003	N	0.178	neutral	None	None	None	None	N
T/M	0.0718	likely_benign	0.081	benign	-0.356	Destabilizing	0.112	N	0.237	neutral	None	None	None	None	N
T/N	0.0953	likely_benign	0.0976	benign	-0.274	Destabilizing	0.011	N	0.178	neutral	N	0.505229062	None	None	N
T/P	0.0933	likely_benign	0.1064	benign	-0.276	Destabilizing	0.026	N	0.339	neutral	N	0.505024382	None	None	N
T/Q	0.1972	likely_benign	0.2063	benign	-0.454	Destabilizing	0.068	N	0.357	neutral	None	None	None	None	N
T/R	0.2456	likely_benign	0.2304	benign	-0.166	Destabilizing	0.035	N	0.395	neutral	None	None	None	None	N
T/S	0.075	likely_benign	0.0767	benign	-0.424	Destabilizing	None	N	0.039	neutral	N	0.492045142	None	None	N
T/V	0.0712	likely_benign	0.0829	benign	-0.276	Destabilizing	0.003	N	0.116	neutral	None	None	None	None	N
T/W	0.5117	ambiguous	0.5446	ambiguous	-1.037	Destabilizing	0.747	D	0.284	neutral	None	None	None	None	N
T/Y	0.205	likely_benign	0.2251	benign	-0.732	Destabilizing	0.204	N	0.393	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.