TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7603	23032;23033;23034	chr2:178721856;178721855;178721854	chr2:179586583;179586582;179586581
N2AB	7286	22081;22082;22083	chr2:178721856;178721855;178721854	chr2:179586583;179586582;179586581
N2A	6359	19300;19301;19302	chr2:178721856;178721855;178721854	chr2:179586583;179586582;179586581
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: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Ig-60
• Domain position: 89
• Structural Position: 175
• Q(SASA): 0.3202
• 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
S/G	None	None	0.001	D	0.081	0.106	0.233785782151	gnomAD-4.0.0	6.92636E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.06595E-07	0	0
S/I	rs777949804	-0.05	0.213	N	0.519	0.252	0.41518383557	gnomAD-2.1.1	4.19E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.18E-06	0
S/I	rs777949804	-0.05	0.213	N	0.519	0.252	0.41518383557	gnomAD-4.0.0	4.85413E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.44414E-06	1.22318E-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
S/A	0.0787	likely_benign	0.0743	benign	-0.675	Destabilizing	0.061	N	0.257	neutral	None	None	None	None	N
S/C	0.1536	likely_benign	0.1542	benign	-0.513	Destabilizing	0.978	D	0.439	neutral	N	0.493494371	None	None	N
S/D	0.2835	likely_benign	0.2643	benign	-0.14	Destabilizing	0.129	N	0.299	neutral	None	None	None	None	N
S/E	0.3999	ambiguous	0.3798	ambiguous	-0.181	Destabilizing	0.01	N	0.137	neutral	None	None	None	None	N
S/F	0.1336	likely_benign	0.1151	benign	-1.018	Destabilizing	0.002	N	0.355	neutral	None	None	None	None	N
S/G	0.0835	likely_benign	0.0897	benign	-0.871	Destabilizing	0.001	N	0.081	neutral	D	0.522477191	None	None	N
S/H	0.2047	likely_benign	0.2031	benign	-1.389	Destabilizing	0.836	D	0.465	neutral	None	None	None	None	N
S/I	0.095	likely_benign	0.0944	benign	-0.272	Destabilizing	0.213	N	0.519	neutral	N	0.434684848	None	None	N
S/K	0.4238	ambiguous	0.4354	ambiguous	-0.656	Destabilizing	0.418	N	0.287	neutral	None	None	None	None	N
S/L	0.0801	likely_benign	0.0771	benign	-0.272	Destabilizing	0.129	N	0.474	neutral	None	None	None	None	N
S/M	0.1444	likely_benign	0.1426	benign	0.061	Stabilizing	0.836	D	0.471	neutral	None	None	None	None	N
S/N	0.0831	likely_benign	0.0814	benign	-0.521	Destabilizing	0.002	N	0.15	neutral	N	0.450134303	None	None	N
S/P	0.7871	likely_pathogenic	0.7409	pathogenic	-0.375	Destabilizing	0.94	D	0.493	neutral	None	None	None	None	N
S/Q	0.3275	likely_benign	0.3322	benign	-0.763	Destabilizing	0.418	N	0.401	neutral	None	None	None	None	N
S/R	0.3175	likely_benign	0.326	benign	-0.49	Destabilizing	0.351	N	0.497	neutral	N	0.443034973	None	None	N
S/T	0.0642	likely_benign	0.0644	benign	-0.601	Destabilizing	0.007	N	0.109	neutral	N	0.398395974	None	None	N
S/V	0.1277	likely_benign	0.1255	benign	-0.375	Destabilizing	0.01	N	0.301	neutral	None	None	None	None	N
S/W	0.2581	likely_benign	0.2419	benign	-0.954	Destabilizing	0.983	D	0.502	neutral	None	None	None	None	N
S/Y	0.1449	likely_benign	0.13	benign	-0.7	Destabilizing	0.557	D	0.52	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.