TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26412	79459;79460;79461	chr2:178566898;178566897;178566896	chr2:179431625;179431624;179431623
N2AB	24771	74536;74537;74538	chr2:178566898;178566897;178566896	chr2:179431625;179431624;179431623
N2A	23844	71755;71756;71757	chr2:178566898;178566897;178566896	chr2:179431625;179431624;179431623
N2B	17347	52264;52265;52266	chr2:178566898;178566897;178566896	chr2:179431625;179431624;179431623
Novex-1	17472	52639;52640;52641	chr2:178566898;178566897;178566896	chr2:179431625;179431624;179431623
Novex-2	17539	52840;52841;52842	chr2:178566898;178566897;178566896	chr2:179431625;179431624;179431623
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Fn3-80
• Domain position: 27
• Structural Position: 29
• Q(SASA): 0.4595
• Predicted PPI site: I

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
S/G	None	None	0.101	N	0.265	0.086	0.162503812791	gnomAD-4.0.0	1.36859E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	3.46741E-04	0	0	0
S/N	rs752040235	0.076	0.002	N	0.139	0.048	0.141422826196	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	4.64E-05	0	0
S/N	rs752040235	0.076	0.002	N	0.139	0.048	0.141422826196	gnomAD-4.0.0	3.42143E-06	None	None	None	None	I	None	0	0	None	0	0	None	1.87322E-05	0	3.59817E-06	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
S/A	0.0888	likely_benign	0.0955	benign	-0.428	Destabilizing	0.004	N	0.055	neutral	None	None	None	None	I
S/C	0.1039	likely_benign	0.1134	benign	-0.24	Destabilizing	0.978	D	0.36	neutral	N	0.480595042	None	None	I
S/D	0.288	likely_benign	0.2846	benign	-0.088	Destabilizing	0.264	N	0.233	neutral	None	None	None	None	I
S/E	0.4763	ambiguous	0.4974	ambiguous	-0.191	Destabilizing	0.418	N	0.22	neutral	None	None	None	None	I
S/F	0.1681	likely_benign	0.1963	benign	-1.082	Destabilizing	0.557	D	0.485	neutral	None	None	None	None	I
S/G	0.11	likely_benign	0.1183	benign	-0.522	Destabilizing	0.101	N	0.265	neutral	N	0.467326179	None	None	I
S/H	0.2946	likely_benign	0.3043	benign	-1.089	Destabilizing	0.005	N	0.219	neutral	None	None	None	None	I
S/I	0.1594	likely_benign	0.1887	benign	-0.308	Destabilizing	0.351	N	0.491	neutral	N	0.47744149	None	None	I
S/K	0.639	likely_pathogenic	0.6733	pathogenic	-0.509	Destabilizing	0.418	N	0.217	neutral	None	None	None	None	I
S/L	0.0979	likely_benign	0.1098	benign	-0.308	Destabilizing	0.129	N	0.404	neutral	None	None	None	None	I
S/M	0.1628	likely_benign	0.1748	benign	0.073	Stabilizing	0.94	D	0.372	neutral	None	None	None	None	I
S/N	0.1067	likely_benign	0.1095	benign	-0.214	Destabilizing	0.002	N	0.139	neutral	N	0.45569676	None	None	I
S/P	0.8458	likely_pathogenic	0.8293	pathogenic	-0.321	Destabilizing	0.94	D	0.455	neutral	None	None	None	None	I
S/Q	0.4581	ambiguous	0.4851	ambiguous	-0.517	Destabilizing	0.716	D	0.345	neutral	None	None	None	None	I
S/R	0.5769	likely_pathogenic	0.6116	pathogenic	-0.274	Destabilizing	0.351	N	0.434	neutral	N	0.51853473	None	None	I
S/T	0.072	likely_benign	0.0725	benign	-0.311	Destabilizing	0.003	N	0.062	neutral	N	0.468068624	None	None	I
S/V	0.1476	likely_benign	0.1657	benign	-0.321	Destabilizing	0.418	N	0.402	neutral	None	None	None	None	I
S/W	0.3964	ambiguous	0.4281	ambiguous	-1.08	Destabilizing	0.951	D	0.421	neutral	None	None	None	None	I
S/Y	0.1835	likely_benign	0.1954	benign	-0.804	Destabilizing	0.002	N	0.259	neutral	None	None	None	None	I

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.