TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4939	15040;15041;15042	chr2:178735631;178735630;178735629	chr2:179600358;179600357;179600356
N2AB	4622	14089;14090;14091	chr2:178735631;178735630;178735629	chr2:179600358;179600357;179600356
N2A	3695	11308;11309;11310	chr2:178735631;178735630;178735629	chr2:179600358;179600357;179600356
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-32
• Domain position: 52
• Structural Position: 130
• Q(SASA): 0.3562
• 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/D	None	None	0.998	N	0.376	0.184	0.479893544335	gnomAD-4.0.0	1.59166E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85843E-06	0	0
E/Q	rs2081311155	None	0.996	N	0.511	0.307	0.518858945281	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/Q	rs2081311155	None	0.996	N	0.511	0.307	0.518858945281	gnomAD-4.0.0	6.57134E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.4699E-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	0.1713	likely_benign	0.1833	benign	-0.468	Destabilizing	0.996	D	0.539	neutral	D	0.57697762	None	None	N
E/C	0.809	likely_pathogenic	0.835	pathogenic	-0.346	Destabilizing	1.0	D	0.667	neutral	None	None	None	None	N
E/D	0.1505	likely_benign	0.1609	benign	-0.358	Destabilizing	0.998	D	0.376	neutral	N	0.50341418	None	None	N
E/F	0.7071	likely_pathogenic	0.7386	pathogenic	-0.153	Destabilizing	1.0	D	0.665	neutral	None	None	None	None	N
E/G	0.1821	likely_benign	0.1953	benign	-0.671	Destabilizing	0.999	D	0.622	neutral	N	0.51438237	None	None	N
E/H	0.3834	ambiguous	0.4072	ambiguous	0.286	Stabilizing	1.0	D	0.607	neutral	None	None	None	None	N
E/I	0.3074	likely_benign	0.3378	benign	0.041	Stabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	N
E/K	0.1143	likely_benign	0.123	benign	0.182	Stabilizing	0.767	D	0.257	neutral	N	0.507653325	None	None	N
E/L	0.3767	ambiguous	0.4084	ambiguous	0.041	Stabilizing	1.0	D	0.696	prob.neutral	None	None	None	None	N
E/M	0.4248	ambiguous	0.454	ambiguous	-0.011	Destabilizing	1.0	D	0.635	neutral	None	None	None	None	N
E/N	0.2725	likely_benign	0.2905	benign	-0.298	Destabilizing	1.0	D	0.617	neutral	None	None	None	None	N
E/P	0.8482	likely_pathogenic	0.8549	pathogenic	-0.11	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	N
E/Q	0.1208	likely_benign	0.126	benign	-0.229	Destabilizing	0.996	D	0.511	neutral	N	0.508699155	None	None	N
E/R	0.1923	likely_benign	0.2052	benign	0.537	Stabilizing	0.998	D	0.595	neutral	None	None	None	None	N
E/S	0.2051	likely_benign	0.2138	benign	-0.446	Destabilizing	0.997	D	0.498	neutral	None	None	None	None	N
E/T	0.1978	likely_benign	0.2099	benign	-0.268	Destabilizing	1.0	D	0.669	neutral	None	None	None	None	N
E/V	0.1944	likely_benign	0.2135	benign	-0.11	Destabilizing	0.999	D	0.686	prob.neutral	D	0.564338338	None	None	N
E/W	0.8128	likely_pathogenic	0.8361	pathogenic	0.063	Stabilizing	1.0	D	0.672	neutral	None	None	None	None	N
E/Y	0.563	ambiguous	0.5968	pathogenic	0.099	Stabilizing	1.0	D	0.671	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.