TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6187	18784;18785;18786	chr2:178729694;178729693;178729692	chr2:179594421;179594420;179594419
N2AB	5870	17833;17834;17835	chr2:178729694;178729693;178729692	chr2:179594421;179594420;179594419
N2A	4943	15052;15053;15054	chr2:178729694;178729693;178729692	chr2:179594421;179594420;179594419
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: A
• RefSeq wild type transcript codon: GCG
• RefSeq wild type template codon: CGC
• Domain: Ig-45
• Domain position: 83
• Structural Position: 166
• Q(SASA): 0.1718
• 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
A/V	rs758380777	-0.092	0.729	N	0.499	0.281	None	gnomAD-2.1.1	2.82E-05	None	None	None	None	N	None	6.47E-05	0	None	0	5.57E-05	None	1.30719E-04	None	0	8.92E-06	0
A/V	rs758380777	-0.092	0.729	N	0.499	0.281	None	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	0	2.07641E-04	0
A/V	rs758380777	-0.092	0.729	N	0.499	0.281	None	gnomAD-4.0.0	7.43705E-06	None	None	None	None	N	None	5.34117E-05	0	None	0	0	None	0	0	2.54304E-06	5.4904E-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
A/C	0.58	likely_pathogenic	0.6505	pathogenic	-0.805	Destabilizing	0.944	D	0.55	neutral	None	None	None	None	N
A/D	0.1552	likely_benign	0.1743	benign	-0.673	Destabilizing	0.116	N	0.545	neutral	None	None	None	None	N
A/E	0.1486	likely_benign	0.1555	benign	-0.73	Destabilizing	0.001	N	0.247	neutral	N	0.521765115	None	None	N
A/F	0.3764	ambiguous	0.4473	ambiguous	-0.93	Destabilizing	0.818	D	0.616	neutral	None	None	None	None	N
A/G	0.1825	likely_benign	0.1943	benign	-0.974	Destabilizing	0.201	N	0.465	neutral	N	0.509169544	None	None	N
A/H	0.4746	ambiguous	0.5042	ambiguous	-1.013	Destabilizing	0.818	D	0.589	neutral	None	None	None	None	N
A/I	0.2371	likely_benign	0.2788	benign	-0.321	Destabilizing	0.69	D	0.577	neutral	None	None	None	None	N
A/K	0.4084	ambiguous	0.4184	ambiguous	-0.943	Destabilizing	0.116	N	0.501	neutral	None	None	None	None	N
A/L	0.2235	likely_benign	0.2534	benign	-0.321	Destabilizing	0.388	N	0.523	neutral	None	None	None	None	N
A/M	0.2454	likely_benign	0.2688	benign	-0.324	Destabilizing	0.932	D	0.546	neutral	None	None	None	None	N
A/N	0.2156	likely_benign	0.25	benign	-0.652	Destabilizing	0.241	N	0.593	neutral	None	None	None	None	N
A/P	0.8625	likely_pathogenic	0.9175	pathogenic	-0.424	Destabilizing	0.492	N	0.563	neutral	D	0.535921079	None	None	N
A/Q	0.2852	likely_benign	0.2794	benign	-0.831	Destabilizing	0.241	N	0.554	neutral	None	None	None	None	N
A/R	0.3795	ambiguous	0.3898	ambiguous	-0.581	Destabilizing	0.388	N	0.547	neutral	None	None	None	None	N
A/S	0.0841	likely_benign	0.0898	benign	-1.022	Destabilizing	0.001	N	0.163	neutral	D	0.53629185	None	None	N
A/T	0.0811	likely_benign	0.085	benign	-0.98	Destabilizing	0.193	N	0.471	neutral	N	0.510857475	None	None	N
A/V	0.1249	likely_benign	0.1369	benign	-0.424	Destabilizing	0.729	D	0.499	neutral	N	0.479859778	None	None	N
A/W	0.7685	likely_pathogenic	0.8229	pathogenic	-1.199	Destabilizing	0.981	D	0.643	neutral	None	None	None	None	N
A/Y	0.475	ambiguous	0.5504	ambiguous	-0.799	Destabilizing	0.818	D	0.616	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.