TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5024	15295;15296;15297	chr2:178734854;178734853;178734852	chr2:179599581;179599580;179599579
N2AB	4707	14344;14345;14346	chr2:178734854;178734853;178734852	chr2:179599581;179599580;179599579
N2A	3780	11563;11564;11565	chr2:178734854;178734853;178734852	chr2:179599581;179599580;179599579
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-33
• Domain position: 44
• Structural Position: 70
• Q(SASA): 0.3317
• 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/A	None	None	0.051	N	0.189	0.141	0.393006254552	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05
E/G	rs2081168482	None	0.625	N	0.307	0.217	0.515995215087	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
E/K	rs750031855	0.099	0.801	N	0.217	0.224	0.430579932962	gnomAD-2.1.1	7.15E-05	None	None	None	None	N	None	0	0	None	0	7.18833E-04	None	1.30753E-04	None	0	1.56E-05	0
E/K	rs750031855	0.099	0.801	N	0.217	0.224	0.430579932962	gnomAD-3.1.2	2.63E-05	None	None	None	None	N	None	0	0	0	0	5.77367E-04	None	0	0	0	2.07125E-04	0
E/K	rs750031855	0.099	0.801	N	0.217	0.224	0.430579932962	gnomAD-4.0.0	1.92116E-05	None	None	None	None	N	None	0	0	None	0	4.45951E-04	None	0	0	2.54286E-06	6.58762E-05	3.20266E-05

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	0.1283	likely_benign	0.1198	benign	-0.142	Destabilizing	0.051	N	0.189	neutral	N	0.483302025	None	None	N
E/C	0.8598	likely_pathogenic	0.8392	pathogenic	0.042	Stabilizing	0.998	D	0.361	neutral	None	None	None	None	N
E/D	0.1233	likely_benign	0.1239	benign	-0.168	Destabilizing	0.005	N	0.161	neutral	N	0.487665168	None	None	N
E/F	0.7307	likely_pathogenic	0.7103	pathogenic	-0.081	Destabilizing	0.991	D	0.362	neutral	None	None	None	None	N
E/G	0.1451	likely_benign	0.1394	benign	-0.315	Destabilizing	0.625	D	0.307	neutral	N	0.514603681	None	None	N
E/H	0.4565	ambiguous	0.4228	ambiguous	0.239	Stabilizing	0.991	D	0.31	neutral	None	None	None	None	N
E/I	0.3836	ambiguous	0.361	ambiguous	0.266	Stabilizing	0.974	D	0.386	neutral	None	None	None	None	N
E/K	0.1413	likely_benign	0.1266	benign	0.497	Stabilizing	0.801	D	0.217	neutral	N	0.508329711	None	None	N
E/L	0.3975	ambiguous	0.3747	ambiguous	0.266	Stabilizing	0.842	D	0.394	neutral	None	None	None	None	N
E/M	0.482	ambiguous	0.4579	ambiguous	0.236	Stabilizing	0.998	D	0.341	neutral	None	None	None	None	N
E/N	0.2475	likely_benign	0.2411	benign	0.224	Stabilizing	0.842	D	0.19	neutral	None	None	None	None	N
E/P	0.3125	likely_benign	0.2831	benign	0.15	Stabilizing	0.016	N	0.207	neutral	None	None	None	None	N
E/Q	0.1427	likely_benign	0.1309	benign	0.261	Stabilizing	0.891	D	0.301	neutral	N	0.508711417	None	None	N
E/R	0.2612	likely_benign	0.2327	benign	0.668	Stabilizing	0.974	D	0.278	neutral	None	None	None	None	N
E/S	0.1749	likely_benign	0.1704	benign	0.066	Stabilizing	0.172	N	0.145	neutral	None	None	None	None	N
E/T	0.2099	likely_benign	0.1946	benign	0.21	Stabilizing	0.728	D	0.315	neutral	None	None	None	None	N
E/V	0.2193	likely_benign	0.2065	benign	0.15	Stabilizing	0.801	D	0.365	neutral	N	0.517385057	None	None	N
E/W	0.9014	likely_pathogenic	0.8856	pathogenic	0.019	Stabilizing	0.998	D	0.447	neutral	None	None	None	None	N
E/Y	0.5864	likely_pathogenic	0.557	ambiguous	0.158	Stabilizing	0.991	D	0.351	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.