TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27809	83650;83651;83652	chr2:178562707;178562706;178562705	chr2:179427434;179427433;179427432
N2AB	26168	78727;78728;78729	chr2:178562707;178562706;178562705	chr2:179427434;179427433;179427432
N2A	25241	75946;75947;75948	chr2:178562707;178562706;178562705	chr2:179427434;179427433;179427432
N2B	18744	56455;56456;56457	chr2:178562707;178562706;178562705	chr2:179427434;179427433;179427432
Novex-1	18869	56830;56831;56832	chr2:178562707;178562706;178562705	chr2:179427434;179427433;179427432
Novex-2	18936	57031;57032;57033	chr2:178562707;178562706;178562705	chr2:179427434;179427433;179427432
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-90
• Domain position: 44
• Structural Position: 54
• Q(SASA): 0.4135
• 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
T/A	None	None	0.017	N	0.303	0.161	0.17948927462	gnomAD-4.0.0	1.63701E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.91863E-06	0	0
T/I	rs922881378	-0.074	0.813	N	0.299	0.274	0.335910606209	gnomAD-2.1.1	8.51E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.84E-05	0
T/I	rs922881378	-0.074	0.813	N	0.299	0.274	0.335910606209	gnomAD-4.0.0	1.63708E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.51067E-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
T/A	0.1209	likely_benign	0.1396	benign	-0.153	Destabilizing	0.017	N	0.303	neutral	N	0.477210969	None	None	N
T/C	0.7313	likely_pathogenic	0.7878	pathogenic	-0.4	Destabilizing	0.98	D	0.353	neutral	None	None	None	None	N
T/D	0.7414	likely_pathogenic	0.8036	pathogenic	-0.007	Destabilizing	0.08	N	0.223	neutral	None	None	None	None	N
T/E	0.6674	likely_pathogenic	0.7464	pathogenic	-0.1	Destabilizing	0.367	N	0.24	neutral	None	None	None	None	N
T/F	0.5816	likely_pathogenic	0.6688	pathogenic	-0.814	Destabilizing	0.979	D	0.405	neutral	None	None	None	None	N
T/G	0.308	likely_benign	0.3285	benign	-0.206	Destabilizing	0.422	N	0.315	neutral	None	None	None	None	N
T/H	0.5385	ambiguous	0.6082	pathogenic	-0.342	Destabilizing	0.852	D	0.401	neutral	None	None	None	None	N
T/I	0.502	ambiguous	0.5816	pathogenic	-0.134	Destabilizing	0.813	D	0.299	neutral	N	0.471395238	None	None	N
T/K	0.5318	ambiguous	0.6164	pathogenic	-0.294	Destabilizing	0.003	N	0.255	neutral	N	0.459721287	None	None	N
T/L	0.2088	likely_benign	0.258	benign	-0.134	Destabilizing	0.622	D	0.242	neutral	None	None	None	None	N
T/M	0.1652	likely_benign	0.2016	benign	-0.166	Destabilizing	0.985	D	0.299	neutral	None	None	None	None	N
T/N	0.2587	likely_benign	0.2949	benign	-0.125	Destabilizing	0.001	N	0.245	neutral	None	None	None	None	N
T/P	0.3869	ambiguous	0.3844	ambiguous	-0.116	Destabilizing	0.74	D	0.273	neutral	N	0.51867359	None	None	N
T/Q	0.4319	ambiguous	0.5054	ambiguous	-0.331	Destabilizing	0.571	D	0.269	neutral	None	None	None	None	N
T/R	0.4896	ambiguous	0.5977	pathogenic	0.004	Stabilizing	0.45	N	0.245	neutral	N	0.505877651	None	None	N
T/S	0.1388	likely_benign	0.1611	benign	-0.288	Destabilizing	0.009	N	0.354	neutral	N	0.434516198	None	None	N
T/V	0.3184	likely_benign	0.3674	ambiguous	-0.116	Destabilizing	0.541	D	0.224	neutral	None	None	None	None	N
T/W	0.8843	likely_pathogenic	0.9082	pathogenic	-0.904	Destabilizing	0.994	D	0.517	neutral	None	None	None	None	N
T/Y	0.6755	likely_pathogenic	0.7452	pathogenic	-0.58	Destabilizing	0.979	D	0.409	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.