TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33051	99376;99377;99378	chr2:178538678;178538677;178538676	chr2:179403405;179403404;179403403
N2AB	31410	94453;94454;94455	chr2:178538678;178538677;178538676	chr2:179403405;179403404;179403403
N2A	30483	91672;91673;91674	chr2:178538678;178538677;178538676	chr2:179403405;179403404;179403403
N2B	23986	72181;72182;72183	chr2:178538678;178538677;178538676	chr2:179403405;179403404;179403403
Novex-1	24111	72556;72557;72558	chr2:178538678;178538677;178538676	chr2:179403405;179403404;179403403
Novex-2	24178	72757;72758;72759	chr2:178538678;178538677;178538676	chr2:179403405;179403404;179403403
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: Fn3-129
• Domain position: 54
• Structural Position: 72
• Q(SASA): 0.77
• 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/K	rs144319649	0.488	0.334	N	0.557	0.178	None	gnomAD-2.1.1	2.81E-05	None	None	None	None	N	None	0	0	None	0	3.89451E-04	None	0	None	0	0	0
E/K	rs144319649	0.488	0.334	N	0.557	0.178	None	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	0	0	0	0	3.85208E-04	None	0	0	1.47E-05	0	0
E/K	rs144319649	0.488	0.334	N	0.557	0.178	None	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	0	None	None	1E-03	0	None	None	None	0	None
E/K	rs144319649	0.488	0.334	N	0.557	0.178	None	gnomAD-4.0.0	1.54916E-05	None	None	None	None	N	None	0	0	None	0	4.67977E-04	None	0	0	2.54293E-06	0	1.60067E-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	0.1754	likely_benign	0.2068	benign	-0.223	Destabilizing	0.334	N	0.582	neutral	N	0.459894645	None	None	N
E/C	0.7164	likely_pathogenic	0.8268	pathogenic	-0.376	Destabilizing	0.982	D	0.726	prob.delet.	None	None	None	None	N
E/D	0.0594	likely_benign	0.0698	benign	-0.342	Destabilizing	0.001	N	0.196	neutral	N	0.455622189	None	None	N
E/F	0.6056	likely_pathogenic	0.7135	pathogenic	0.034	Stabilizing	0.982	D	0.671	neutral	None	None	None	None	N
E/G	0.1629	likely_benign	0.1893	benign	-0.41	Destabilizing	0.334	N	0.495	neutral	N	0.445522625	None	None	N
E/H	0.4332	ambiguous	0.5222	ambiguous	0.572	Stabilizing	0.947	D	0.643	neutral	None	None	None	None	N
E/I	0.2867	likely_benign	0.3784	ambiguous	0.238	Stabilizing	0.826	D	0.683	prob.neutral	None	None	None	None	N
E/K	0.2754	likely_benign	0.2956	benign	0.265	Stabilizing	0.334	N	0.557	neutral	N	0.467916696	None	None	N
E/L	0.3292	likely_benign	0.4207	ambiguous	0.238	Stabilizing	0.7	D	0.667	neutral	None	None	None	None	N
E/M	0.4268	ambiguous	0.5	ambiguous	0.003	Stabilizing	0.982	D	0.645	neutral	None	None	None	None	N
E/N	0.1386	likely_benign	0.1838	benign	-0.208	Destabilizing	0.539	D	0.592	neutral	None	None	None	None	N
E/P	0.7888	likely_pathogenic	0.8522	pathogenic	0.104	Stabilizing	0.826	D	0.626	neutral	None	None	None	None	N
E/Q	0.186	likely_benign	0.1986	benign	-0.14	Destabilizing	0.638	D	0.587	neutral	N	0.440020805	None	None	N
E/R	0.4035	ambiguous	0.4519	ambiguous	0.631	Stabilizing	0.7	D	0.638	neutral	None	None	None	None	N
E/S	0.1661	likely_benign	0.2059	benign	-0.341	Destabilizing	0.25	N	0.555	neutral	None	None	None	None	N
E/T	0.1986	likely_benign	0.2396	benign	-0.174	Destabilizing	0.7	D	0.574	neutral	None	None	None	None	N
E/V	0.1794	likely_benign	0.2228	benign	0.104	Stabilizing	0.781	D	0.623	neutral	N	0.429091735	None	None	N
E/W	0.8524	likely_pathogenic	0.9066	pathogenic	0.19	Stabilizing	0.982	D	0.73	prob.delet.	None	None	None	None	N
E/Y	0.4159	ambiguous	0.543	ambiguous	0.277	Stabilizing	0.982	D	0.643	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.