TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7088	21487;21488;21489	chr2:178723997;178723996;178723995	chr2:179588724;179588723;179588722
N2AB	6771	20536;20537;20538	chr2:178723997;178723996;178723995	chr2:179588724;179588723;179588722
N2A	5844	17755;17756;17757	chr2:178723997;178723996;178723995	chr2:179588724;179588723;179588722
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: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-55
• Domain position: 45
• Structural Position: 102
• Q(SASA): 0.4131
• 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
A/T	None	None	0.425	N	0.175	0.127	0.149567049428	gnomAD-4.0.0	3.18375E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85948E-06	0	3.0259E-05

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
A/C	0.4405	ambiguous	0.4415	ambiguous	-0.791	Destabilizing	0.995	D	0.303	neutral	None	None	None	None	N
A/D	0.109	likely_benign	0.1093	benign	-0.546	Destabilizing	0.003	N	0.166	neutral	None	None	None	None	N
A/E	0.1003	likely_benign	0.1025	benign	-0.7	Destabilizing	0.001	N	0.137	neutral	N	0.409318604	None	None	N
A/F	0.2154	likely_benign	0.2061	benign	-0.865	Destabilizing	0.944	D	0.389	neutral	None	None	None	None	N
A/G	0.1019	likely_benign	0.1004	benign	-0.193	Destabilizing	0.425	N	0.208	neutral	N	0.403237994	None	None	N
A/H	0.2787	likely_benign	0.2703	benign	-0.157	Destabilizing	0.007	N	0.173	neutral	None	None	None	None	N
A/I	0.1522	likely_benign	0.1418	benign	-0.348	Destabilizing	0.944	D	0.425	neutral	None	None	None	None	N
A/K	0.1808	likely_benign	0.1838	benign	-0.535	Destabilizing	0.329	N	0.326	neutral	None	None	None	None	N
A/L	0.1088	likely_benign	0.1093	benign	-0.348	Destabilizing	0.704	D	0.31	neutral	None	None	None	None	N
A/M	0.1604	likely_benign	0.1493	benign	-0.502	Destabilizing	0.981	D	0.31	neutral	None	None	None	None	N
A/N	0.1301	likely_benign	0.1282	benign	-0.215	Destabilizing	0.543	D	0.305	neutral	None	None	None	None	N
A/P	0.083	likely_benign	0.0824	benign	-0.266	Destabilizing	0.006	N	0.19	neutral	N	0.380747923	None	None	N
A/Q	0.1557	likely_benign	0.1602	benign	-0.495	Destabilizing	0.085	N	0.186	neutral	None	None	None	None	N
A/R	0.1655	likely_benign	0.1711	benign	-0.069	Destabilizing	0.704	D	0.325	neutral	None	None	None	None	N
A/S	0.075	likely_benign	0.0775	benign	-0.396	Destabilizing	0.425	N	0.203	neutral	N	0.397832174	None	None	N
A/T	0.0725	likely_benign	0.0712	benign	-0.477	Destabilizing	0.425	N	0.175	neutral	N	0.458016628	None	None	N
A/V	0.0895	likely_benign	0.0866	benign	-0.266	Destabilizing	0.784	D	0.171	neutral	N	0.47746918	None	None	N
A/W	0.4484	ambiguous	0.4404	ambiguous	-0.968	Destabilizing	0.995	D	0.394	neutral	None	None	None	None	N
A/Y	0.2941	likely_benign	0.2787	benign	-0.643	Destabilizing	0.893	D	0.451	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.