TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25937	78034;78035;78036	chr2:178568323;178568322;178568321	chr2:179433050;179433049;179433048
N2AB	24296	73111;73112;73113	chr2:178568323;178568322;178568321	chr2:179433050;179433049;179433048
N2A	23369	70330;70331;70332	chr2:178568323;178568322;178568321	chr2:179433050;179433049;179433048
N2B	16872	50839;50840;50841	chr2:178568323;178568322;178568321	chr2:179433050;179433049;179433048
Novex-1	16997	51214;51215;51216	chr2:178568323;178568322;178568321	chr2:179433050;179433049;179433048
Novex-2	17064	51415;51416;51417	chr2:178568323;178568322;178568321	chr2:179433050;179433049;179433048
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Fn3-76
• Domain position: 48
• Structural Position: 64
• Q(SASA): 0.4971
• 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
V/A	None	None	0.024	N	0.235	0.065	0.44143026662	gnomAD-4.0.0	1.59202E-06	None	None	None	None	N	None	0	0	None	0	2.77886E-05	None	0	0	0	0	0
V/I	None	None	None	N	0.164	0.082	0.425028116352	gnomAD-4.0.0	3.18408E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85943E-06	0	3.02608E-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
V/A	0.1053	likely_benign	0.1075	benign	-0.623	Destabilizing	0.024	N	0.235	neutral	N	0.409388467	None	None	N
V/C	0.5574	ambiguous	0.5564	ambiguous	-0.525	Destabilizing	0.864	D	0.286	neutral	None	None	None	None	N
V/D	0.3165	likely_benign	0.3258	benign	-0.362	Destabilizing	0.038	N	0.327	neutral	None	None	None	None	N
V/E	0.2893	likely_benign	0.2887	benign	-0.473	Destabilizing	0.055	N	0.311	neutral	N	0.404883937	None	None	N
V/F	0.1419	likely_benign	0.1597	benign	-0.802	Destabilizing	0.12	N	0.331	neutral	None	None	None	None	N
V/G	0.1625	likely_benign	0.1695	benign	-0.775	Destabilizing	0.024	N	0.318	neutral	N	0.447578709	None	None	N
V/H	0.388	ambiguous	0.4008	ambiguous	-0.311	Destabilizing	0.356	N	0.346	neutral	None	None	None	None	N
V/I	0.0684	likely_benign	0.0732	benign	-0.37	Destabilizing	None	N	0.164	neutral	N	0.473631946	None	None	N
V/K	0.3002	likely_benign	0.2923	benign	-0.478	Destabilizing	0.072	N	0.312	neutral	None	None	None	None	N
V/L	0.1227	likely_benign	0.1308	benign	-0.37	Destabilizing	None	N	0.104	neutral	N	0.46935949	None	None	N
V/M	0.0978	likely_benign	0.1021	benign	-0.346	Destabilizing	0.214	N	0.259	neutral	None	None	None	None	N
V/N	0.1201	likely_benign	0.1304	benign	-0.149	Destabilizing	None	N	0.202	neutral	None	None	None	None	N
V/P	0.7644	likely_pathogenic	0.8355	pathogenic	-0.419	Destabilizing	0.628	D	0.357	neutral	None	None	None	None	N
V/Q	0.2353	likely_benign	0.2285	benign	-0.416	Destabilizing	0.356	N	0.353	neutral	None	None	None	None	N
V/R	0.2944	likely_benign	0.2933	benign	0.075	Stabilizing	0.136	N	0.385	neutral	None	None	None	None	N
V/S	0.1069	likely_benign	0.1109	benign	-0.526	Destabilizing	0.031	N	0.285	neutral	None	None	None	None	N
V/T	0.098	likely_benign	0.1043	benign	-0.537	Destabilizing	0.031	N	0.243	neutral	None	None	None	None	N
V/W	0.7539	likely_pathogenic	0.7857	pathogenic	-0.872	Destabilizing	0.864	D	0.361	neutral	None	None	None	None	N
V/Y	0.4189	ambiguous	0.4304	ambiguous	-0.579	Destabilizing	0.356	N	0.306	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.