TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22405	67438;67439;67440	chr2:178580074;178580073;178580072	chr2:179444801;179444800;179444799
N2AB	20764	62515;62516;62517	chr2:178580074;178580073;178580072	chr2:179444801;179444800;179444799
N2A	19837	59734;59735;59736	chr2:178580074;178580073;178580072	chr2:179444801;179444800;179444799
N2B	13340	40243;40244;40245	chr2:178580074;178580073;178580072	chr2:179444801;179444800;179444799
Novex-1	13465	40618;40619;40620	chr2:178580074;178580073;178580072	chr2:179444801;179444800;179444799
Novex-2	13532	40819;40820;40821	chr2:178580074;178580073;178580072	chr2:179444801;179444800;179444799
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: Fn3-50
• Domain position: 52
• Structural Position: 69
• Q(SASA): 0.1252
• 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/I	rs751337482	-0.06	0.627	N	0.455	0.25	0.363751660372	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
T/I	rs751337482	-0.06	0.627	N	0.455	0.25	0.363751660372	gnomAD-4.0.0	1.36874E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.31895E-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	0.1228	likely_benign	0.1215	benign	-1.026	Destabilizing	0.001	N	0.113	neutral	N	0.47192258	None	None	N
T/C	0.5498	ambiguous	0.4857	ambiguous	-0.661	Destabilizing	0.944	D	0.439	neutral	None	None	None	None	N
T/D	0.7167	likely_pathogenic	0.6956	pathogenic	-0.22	Destabilizing	0.388	N	0.397	neutral	None	None	None	None	N
T/E	0.7097	likely_pathogenic	0.6901	pathogenic	-0.185	Destabilizing	0.241	N	0.411	neutral	None	None	None	None	N
T/F	0.6586	likely_pathogenic	0.6462	pathogenic	-1.079	Destabilizing	0.818	D	0.479	neutral	None	None	None	None	N
T/G	0.4339	ambiguous	0.4166	ambiguous	-1.313	Destabilizing	0.116	N	0.409	neutral	None	None	None	None	N
T/H	0.6352	likely_pathogenic	0.6035	pathogenic	-1.544	Destabilizing	0.818	D	0.461	neutral	None	None	None	None	N
T/I	0.5572	ambiguous	0.4709	ambiguous	-0.343	Destabilizing	0.627	D	0.455	neutral	N	0.474726601	None	None	N
T/K	0.6599	likely_pathogenic	0.6382	pathogenic	-0.692	Destabilizing	0.001	N	0.225	neutral	N	0.472902948	None	None	N
T/L	0.317	likely_benign	0.2768	benign	-0.343	Destabilizing	0.241	N	0.408	neutral	None	None	None	None	N
T/M	0.2081	likely_benign	0.1789	benign	-0.074	Destabilizing	0.818	D	0.455	neutral	None	None	None	None	N
T/N	0.2911	likely_benign	0.2704	benign	-0.769	Destabilizing	0.388	N	0.441	neutral	None	None	None	None	N
T/P	0.8581	likely_pathogenic	0.8947	pathogenic	-0.538	Destabilizing	0.324	N	0.442	neutral	N	0.479285731	None	None	N
T/Q	0.5633	ambiguous	0.5342	ambiguous	-0.868	Destabilizing	0.69	D	0.451	neutral	None	None	None	None	N
T/R	0.6173	likely_pathogenic	0.6114	pathogenic	-0.529	Destabilizing	0.193	N	0.44	neutral	N	0.479486314	None	None	N
T/S	0.1509	likely_benign	0.1423	benign	-1.103	Destabilizing	0.003	N	0.131	neutral	N	0.458721209	None	None	N
T/V	0.3658	ambiguous	0.2967	benign	-0.538	Destabilizing	0.241	N	0.41	neutral	None	None	None	None	N
T/W	0.9254	likely_pathogenic	0.9264	pathogenic	-0.991	Destabilizing	0.981	D	0.497	neutral	None	None	None	None	N
T/Y	0.7124	likely_pathogenic	0.7031	pathogenic	-0.746	Destabilizing	0.932	D	0.49	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.