TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25310	76153;76154;76155	chr2:178570204;178570203;178570202	chr2:179434931;179434930;179434929
N2AB	23669	71230;71231;71232	chr2:178570204;178570203;178570202	chr2:179434931;179434930;179434929
N2A	22742	68449;68450;68451	chr2:178570204;178570203;178570202	chr2:179434931;179434930;179434929
N2B	16245	48958;48959;48960	chr2:178570204;178570203;178570202	chr2:179434931;179434930;179434929
Novex-1	16370	49333;49334;49335	chr2:178570204;178570203;178570202	chr2:179434931;179434930;179434929
Novex-2	16437	49534;49535;49536	chr2:178570204;178570203;178570202	chr2:179434931;179434930;179434929
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Fn3-72
• Domain position: 7
• Structural Position: 7
• Q(SASA): 0.4815
• 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/S	rs1559387965	None	0.285	N	0.369	0.083	0.218845423259	gnomAD-4.0.0	1.36868E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79915E-06	0	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
A/C	0.2824	likely_benign	0.3399	benign	-0.945	Destabilizing	0.991	D	0.429	neutral	None	None	None	None	N
A/D	0.2161	likely_benign	0.2303	benign	-1.889	Destabilizing	0.001	N	0.243	neutral	N	0.40894575	None	None	N
A/E	0.1686	likely_benign	0.1768	benign	-1.96	Destabilizing	0.017	N	0.197	neutral	None	None	None	None	N
A/F	0.2133	likely_benign	0.2506	benign	-1.295	Destabilizing	0.965	D	0.459	neutral	None	None	None	None	N
A/G	0.1241	likely_benign	0.1313	benign	-1.274	Destabilizing	0.285	N	0.331	neutral	N	0.42995574	None	None	N
A/H	0.3218	likely_benign	0.3729	ambiguous	-1.424	Destabilizing	0.901	D	0.443	neutral	None	None	None	None	N
A/I	0.1143	likely_benign	0.1391	benign	-0.657	Destabilizing	0.901	D	0.475	neutral	None	None	None	None	N
A/K	0.2803	likely_benign	0.3101	benign	-1.382	Destabilizing	0.39	N	0.423	neutral	None	None	None	None	N
A/L	0.1019	likely_benign	0.1242	benign	-0.657	Destabilizing	0.561	D	0.398	neutral	None	None	None	None	N
A/M	0.1161	likely_benign	0.1446	benign	-0.408	Destabilizing	0.965	D	0.409	neutral	None	None	None	None	N
A/N	0.1617	likely_benign	0.1874	benign	-1.06	Destabilizing	0.017	N	0.312	neutral	None	None	None	None	N
A/P	0.0936	likely_benign	0.1016	benign	-0.757	Destabilizing	0.003	N	0.241	neutral	N	0.418933457	None	None	N
A/Q	0.2087	likely_benign	0.2332	benign	-1.335	Destabilizing	0.047	N	0.241	neutral	None	None	None	None	N
A/R	0.2926	likely_benign	0.3164	benign	-0.903	Destabilizing	0.561	D	0.458	neutral	None	None	None	None	N
A/S	0.0855	likely_benign	0.0926	benign	-1.271	Destabilizing	0.285	N	0.369	neutral	N	0.420472252	None	None	N
A/T	0.071	likely_benign	0.0761	benign	-1.278	Destabilizing	0.491	N	0.311	neutral	N	0.410679333	None	None	N
A/V	0.0764	likely_benign	0.0838	benign	-0.757	Destabilizing	0.662	D	0.307	neutral	N	0.478712479	None	None	N
A/W	0.5847	likely_pathogenic	0.6332	pathogenic	-1.576	Destabilizing	0.991	D	0.595	neutral	None	None	None	None	N
A/Y	0.2729	likely_benign	0.3203	benign	-1.242	Destabilizing	0.965	D	0.463	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.