TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28342	85249;85250;85251	chr2:178561108;178561107;178561106	chr2:179425835;179425834;179425833
N2AB	26701	80326;80327;80328	chr2:178561108;178561107;178561106	chr2:179425835;179425834;179425833
N2A	25774	77545;77546;77547	chr2:178561108;178561107;178561106	chr2:179425835;179425834;179425833
N2B	19277	58054;58055;58056	chr2:178561108;178561107;178561106	chr2:179425835;179425834;179425833
Novex-1	19402	58429;58430;58431	chr2:178561108;178561107;178561106	chr2:179425835;179425834;179425833
Novex-2	19469	58630;58631;58632	chr2:178561108;178561107;178561106	chr2:179425835;179425834;179425833
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCC
• RefSeq wild type template codon: AGG
• Domain: Fn3-94
• Domain position: 91
• Structural Position: 123
• Q(SASA): 0.3149
• 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/P	None	None	0.938	N	0.595	0.243	0.193865811164	gnomAD-4.0.0	1.59116E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43271E-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	0.1237	likely_benign	0.1316	benign	-0.881	Destabilizing	0.307	N	0.494	neutral	N	0.472050292	None	None	N
S/C	0.1461	likely_benign	0.1714	benign	-0.618	Destabilizing	0.994	D	0.597	neutral	N	0.471111614	None	None	N
S/D	0.7127	likely_pathogenic	0.7586	pathogenic	-0.366	Destabilizing	0.74	D	0.523	neutral	None	None	None	None	N
S/E	0.7985	likely_pathogenic	0.835	pathogenic	-0.367	Destabilizing	0.74	D	0.516	neutral	None	None	None	None	N
S/F	0.6092	likely_pathogenic	0.6709	pathogenic	-1.015	Destabilizing	0.883	D	0.681	prob.neutral	N	0.485074812	None	None	N
S/G	0.1556	likely_benign	0.1584	benign	-1.128	Destabilizing	0.74	D	0.46	neutral	None	None	None	None	N
S/H	0.6778	likely_pathogenic	0.7256	pathogenic	-1.517	Destabilizing	0.996	D	0.587	neutral	None	None	None	None	N
S/I	0.2992	likely_benign	0.3402	ambiguous	-0.326	Destabilizing	0.587	D	0.665	prob.neutral	None	None	None	None	N
S/K	0.8799	likely_pathogenic	0.9169	pathogenic	-0.734	Destabilizing	0.74	D	0.51	neutral	None	None	None	None	N
S/L	0.24	likely_benign	0.2759	benign	-0.326	Destabilizing	0.587	D	0.635	neutral	None	None	None	None	N
S/M	0.3374	likely_benign	0.3515	ambiguous	-0.03	Destabilizing	0.953	D	0.609	neutral	None	None	None	None	N
S/N	0.248	likely_benign	0.2881	benign	-0.681	Destabilizing	0.74	D	0.551	neutral	None	None	None	None	N
S/P	0.1441	likely_benign	0.162	benign	-0.478	Destabilizing	0.938	D	0.595	neutral	N	0.438532364	None	None	N
S/Q	0.7753	likely_pathogenic	0.8098	pathogenic	-0.878	Destabilizing	0.953	D	0.507	neutral	None	None	None	None	N
S/R	0.8833	likely_pathogenic	0.9169	pathogenic	-0.572	Destabilizing	0.953	D	0.587	neutral	None	None	None	None	N
S/T	0.1208	likely_benign	0.1194	benign	-0.733	Destabilizing	0.012	N	0.289	neutral	N	0.466855116	None	None	N
S/V	0.2858	likely_benign	0.316	benign	-0.478	Destabilizing	0.009	N	0.553	neutral	None	None	None	None	N
S/W	0.7391	likely_pathogenic	0.784	pathogenic	-0.939	Destabilizing	0.996	D	0.773	deleterious	None	None	None	None	N
S/Y	0.5134	ambiguous	0.5924	pathogenic	-0.698	Destabilizing	0.938	D	0.683	prob.neutral	N	0.484821323	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.