TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23714	71365;71366;71367	chr2:178574992;178574991;178574990	chr2:179439719;179439718;179439717
N2AB	22073	66442;66443;66444	chr2:178574992;178574991;178574990	chr2:179439719;179439718;179439717
N2A	21146	63661;63662;63663	chr2:178574992;178574991;178574990	chr2:179439719;179439718;179439717
N2B	14649	44170;44171;44172	chr2:178574992;178574991;178574990	chr2:179439719;179439718;179439717
Novex-1	14774	44545;44546;44547	chr2:178574992;178574991;178574990	chr2:179439719;179439718;179439717
Novex-2	14841	44746;44747;44748	chr2:178574992;178574991;178574990	chr2:179439719;179439718;179439717
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-130
• Domain position: 78
• Structural Position: 165
• Q(SASA): 0.5765
• Predicted PPI site: I

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	rs767016969	0.734	0.549	N	0.361	0.248	0.268211541103	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	0	1.66389E-04
E/K	rs767016969	0.734	0.549	N	0.361	0.248	0.268211541103	gnomAD-4.0.0	6.84398E-06	None	None	None	None	I	None	2.98882E-05	2.23734E-05	None	0	0	None	0	0	5.39758E-06	0	3.31466E-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	0.168	likely_benign	0.1553	benign	-0.287	Destabilizing	0.201	N	0.446	neutral	N	0.489570805	None	None	I
E/C	0.8292	likely_pathogenic	0.822	pathogenic	0.028	Stabilizing	0.992	D	0.519	neutral	None	None	None	None	I
E/D	0.1709	likely_benign	0.1664	benign	-0.319	Destabilizing	0.004	N	0.23	neutral	N	0.494610461	None	None	I
E/F	0.7868	likely_pathogenic	0.7507	pathogenic	-0.253	Destabilizing	0.85	D	0.506	neutral	None	None	None	None	I
E/G	0.2594	likely_benign	0.251	benign	-0.451	Destabilizing	0.549	D	0.503	neutral	N	0.515121026	None	None	I
E/H	0.4886	ambiguous	0.4517	ambiguous	0.05	Stabilizing	0.972	D	0.401	neutral	None	None	None	None	I
E/I	0.3564	ambiguous	0.3275	benign	0.1	Stabilizing	0.447	N	0.533	neutral	None	None	None	None	I
E/K	0.2083	likely_benign	0.1768	benign	0.496	Stabilizing	0.549	D	0.361	neutral	N	0.507006306	None	None	I
E/L	0.4713	ambiguous	0.4377	ambiguous	0.1	Stabilizing	0.447	N	0.509	neutral	None	None	None	None	I
E/M	0.4273	ambiguous	0.3943	ambiguous	0.148	Stabilizing	0.92	D	0.5	neutral	None	None	None	None	I
E/N	0.2753	likely_benign	0.2734	benign	0.169	Stabilizing	0.447	N	0.389	neutral	None	None	None	None	I
E/P	0.8657	likely_pathogenic	0.856	pathogenic	-0.009	Destabilizing	0.92	D	0.435	neutral	None	None	None	None	I
E/Q	0.1476	likely_benign	0.1381	benign	0.188	Stabilizing	0.712	D	0.396	neutral	D	0.525517496	None	None	I
E/R	0.3672	ambiguous	0.3175	benign	0.641	Stabilizing	0.92	D	0.383	neutral	None	None	None	None	I
E/S	0.1736	likely_benign	0.1713	benign	0.046	Stabilizing	0.25	N	0.331	neutral	None	None	None	None	I
E/T	0.1662	likely_benign	0.1611	benign	0.184	Stabilizing	0.009	N	0.24	neutral	None	None	None	None	I
E/V	0.2049	likely_benign	0.1867	benign	-0.009	Destabilizing	0.004	N	0.348	neutral	N	0.489775069	None	None	I
E/W	0.931	likely_pathogenic	0.9151	pathogenic	-0.133	Destabilizing	0.992	D	0.561	neutral	None	None	None	None	I
E/Y	0.678	likely_pathogenic	0.6486	pathogenic	-0.01	Destabilizing	0.92	D	0.495	neutral	None	None	None	None	I

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.