TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	10020	30283;30284;30285	chr2:178704312;178704311;178704310	chr2:179569039;179569038;179569037
N2AB	9703	29332;29333;29334	chr2:178704312;178704311;178704310	chr2:179569039;179569038;179569037
N2A	8776	26551;26552;26553	chr2:178704312;178704311;178704310	chr2:179569039;179569038;179569037
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-85
• Domain position: 32
• Structural Position: 47
• Q(SASA): 0.3866
• 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	rs764487564	-0.974	0.012	None	0.515	0.115	0.351830644314	gnomAD-2.1.1	4.01E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
E/D	rs764487564	-0.974	0.012	None	0.515	0.115	0.351830644314	gnomAD-4.0.0	6.84135E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.15931E-05	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	0.2071	likely_benign	0.3393	benign	-0.734	Destabilizing	0.012	N	0.457	neutral	None	None	None	None	N
E/C	0.9072	likely_pathogenic	0.9664	pathogenic	-0.514	Destabilizing	0.676	D	0.588	neutral	None	None	None	None	N
E/D	0.2471	likely_benign	0.3847	ambiguous	-0.88	Destabilizing	0.012	N	0.515	neutral	None	None	None	None	N
E/F	0.8285	likely_pathogenic	0.9314	pathogenic	0.037	Stabilizing	0.356	N	0.598	neutral	None	None	None	None	N
E/G	0.3267	likely_benign	0.5459	ambiguous	-1.089	Destabilizing	0.012	N	0.531	neutral	None	None	None	None	N
E/H	0.4987	ambiguous	0.7157	pathogenic	-0.029	Destabilizing	0.356	N	0.598	neutral	None	None	None	None	N
E/I	0.3744	ambiguous	0.574	pathogenic	0.233	Stabilizing	0.214	N	0.611	neutral	None	None	None	None	N
E/K	0.119	likely_benign	0.2166	benign	-0.462	Destabilizing	None	N	0.213	neutral	None	None	None	None	N
E/L	0.4534	ambiguous	0.6971	pathogenic	0.233	Stabilizing	0.072	N	0.557	neutral	None	None	None	None	N
E/M	0.4809	ambiguous	0.6797	pathogenic	0.483	Stabilizing	0.356	N	0.579	neutral	None	None	None	None	N
E/N	0.3122	likely_benign	0.5311	ambiguous	-1.042	Destabilizing	0.038	N	0.555	neutral	None	None	None	None	N
E/P	0.954	likely_pathogenic	0.9849	pathogenic	-0.068	Destabilizing	0.072	N	0.588	neutral	None	None	None	None	N
E/Q	0.1115	likely_benign	0.1825	benign	-0.879	Destabilizing	None	N	0.218	neutral	None	None	None	None	N
E/R	0.2292	likely_benign	0.3977	ambiguous	-0.062	Destabilizing	0.038	N	0.569	neutral	None	None	None	None	N
E/S	0.249	likely_benign	0.4196	ambiguous	-1.311	Destabilizing	None	N	0.206	neutral	None	None	None	None	N
E/T	0.2301	likely_benign	0.3865	ambiguous	-1.005	Destabilizing	0.038	N	0.559	neutral	None	None	None	None	N
E/V	0.2259	likely_benign	0.3664	ambiguous	-0.068	Destabilizing	0.055	N	0.561	neutral	None	None	None	None	N
E/W	0.9363	likely_pathogenic	0.9751	pathogenic	0.355	Stabilizing	0.864	D	0.603	neutral	None	None	None	None	N
E/Y	0.7093	likely_pathogenic	0.8737	pathogenic	0.301	Stabilizing	0.356	N	0.605	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.