TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25747	77464;77465;77466	chr2:178568893;178568892;178568891	chr2:179433620;179433619;179433618
N2AB	24106	72541;72542;72543	chr2:178568893;178568892;178568891	chr2:179433620;179433619;179433618
N2A	23179	69760;69761;69762	chr2:178568893;178568892;178568891	chr2:179433620;179433619;179433618
N2B	16682	50269;50270;50271	chr2:178568893;178568892;178568891	chr2:179433620;179433619;179433618
Novex-1	16807	50644;50645;50646	chr2:178568893;178568892;178568891	chr2:179433620;179433619;179433618
Novex-2	16874	50845;50846;50847	chr2:178568893;178568892;178568891	chr2:179433620;179433619;179433618
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: Fn3-75
• Domain position: 50
• Structural Position: 67
• Q(SASA): 0.6087
• 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/Q	rs762636595	0.289	0.491	N	0.457	0.152	0.184867976434	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
E/Q	rs762636595	0.289	0.491	N	0.457	0.152	0.184867976434	gnomAD-4.0.0	2.05334E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79922E-06	1.15974E-05	0
E/V	None	None	0.005	N	0.274	0.223	0.315609569513	gnomAD-4.0.0	6.84445E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99617E-07	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	0.1829	likely_benign	0.1674	benign	-0.629	Destabilizing	0.285	N	0.511	neutral	N	0.440735668	None	None	N
E/C	0.874	likely_pathogenic	0.8536	pathogenic	-0.112	Destabilizing	0.991	D	0.559	neutral	None	None	None	None	N
E/D	0.2406	likely_benign	0.196	benign	-0.684	Destabilizing	0.003	N	0.19	neutral	N	0.443602615	None	None	N
E/F	0.829	likely_pathogenic	0.7842	pathogenic	-0.473	Destabilizing	0.818	D	0.565	neutral	None	None	None	None	N
E/G	0.3798	ambiguous	0.3275	benign	-0.88	Destabilizing	0.491	N	0.548	neutral	N	0.480216776	None	None	N
E/H	0.6704	likely_pathogenic	0.6026	pathogenic	-0.497	Destabilizing	0.009	N	0.277	neutral	None	None	None	None	N
E/I	0.3122	likely_benign	0.2905	benign	0.016	Stabilizing	0.209	N	0.536	neutral	None	None	None	None	N
E/K	0.3527	ambiguous	0.3027	benign	0.026	Stabilizing	0.491	N	0.422	neutral	N	0.427094367	None	None	N
E/L	0.4445	ambiguous	0.4006	ambiguous	0.016	Stabilizing	0.002	N	0.347	neutral	None	None	None	None	N
E/M	0.5253	ambiguous	0.4798	ambiguous	0.316	Stabilizing	0.818	D	0.56	neutral	None	None	None	None	N
E/N	0.4594	ambiguous	0.3808	ambiguous	-0.31	Destabilizing	0.39	N	0.473	neutral	None	None	None	None	N
E/P	0.4875	ambiguous	0.4073	ambiguous	-0.179	Destabilizing	0.901	D	0.596	neutral	None	None	None	None	N
E/Q	0.2121	likely_benign	0.1942	benign	-0.276	Destabilizing	0.491	N	0.457	neutral	N	0.409412684	None	None	N
E/R	0.504	ambiguous	0.459	ambiguous	0.214	Stabilizing	0.818	D	0.491	neutral	None	None	None	None	N
E/S	0.3019	likely_benign	0.2619	benign	-0.509	Destabilizing	0.561	D	0.42	neutral	None	None	None	None	N
E/T	0.2472	likely_benign	0.2295	benign	-0.308	Destabilizing	0.561	D	0.528	neutral	None	None	None	None	N
E/V	0.1786	likely_benign	0.1728	benign	-0.179	Destabilizing	0.005	N	0.274	neutral	N	0.398099612	None	None	N
E/W	0.9606	likely_pathogenic	0.9481	pathogenic	-0.288	Destabilizing	0.991	D	0.581	neutral	None	None	None	None	N
E/Y	0.7687	likely_pathogenic	0.7092	pathogenic	-0.221	Destabilizing	0.692	D	0.573	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.