TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27628	83107;83108;83109	chr2:178563250;178563249;178563248	chr2:179427977;179427976;179427975
N2AB	25987	78184;78185;78186	chr2:178563250;178563249;178563248	chr2:179427977;179427976;179427975
N2A	25060	75403;75404;75405	chr2:178563250;178563249;178563248	chr2:179427977;179427976;179427975
N2B	18563	55912;55913;55914	chr2:178563250;178563249;178563248	chr2:179427977;179427976;179427975
Novex-1	18688	56287;56288;56289	chr2:178563250;178563249;178563248	chr2:179427977;179427976;179427975
Novex-2	18755	56488;56489;56490	chr2:178563250;178563249;178563248	chr2:179427977;179427976;179427975
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Fn3-89
• Domain position: 59
• Structural Position: 88
• Q(SASA): 0.2902
• 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
G/R	rs773909467	-0.312	0.984	N	0.689	0.281	0.456089687795	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	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
G/A	0.0949	likely_benign	0.0973	benign	-0.412	Destabilizing	0.011	N	0.251	neutral	N	0.406884092	None	None	N
G/C	0.1821	likely_benign	0.1872	benign	-0.456	Destabilizing	0.999	D	0.727	prob.delet.	None	None	None	None	N
G/D	0.215	likely_benign	0.2088	benign	-0.911	Destabilizing	0.976	D	0.583	neutral	None	None	None	None	N
G/E	0.1948	likely_benign	0.1836	benign	-0.866	Destabilizing	0.968	D	0.643	neutral	N	0.421736115	None	None	N
G/F	0.5262	ambiguous	0.5463	ambiguous	-0.618	Destabilizing	0.988	D	0.715	prob.delet.	None	None	None	None	N
G/H	0.3662	ambiguous	0.3727	ambiguous	-1.011	Destabilizing	0.999	D	0.709	prob.delet.	None	None	None	None	N
G/I	0.223	likely_benign	0.2324	benign	0.182	Stabilizing	0.976	D	0.707	prob.neutral	None	None	None	None	N
G/K	0.3812	ambiguous	0.3616	ambiguous	-0.747	Destabilizing	0.976	D	0.641	neutral	None	None	None	None	N
G/L	0.2943	likely_benign	0.2963	benign	0.182	Stabilizing	0.919	D	0.651	neutral	None	None	None	None	N
G/M	0.3391	likely_benign	0.3507	ambiguous	-0.037	Destabilizing	0.999	D	0.729	prob.delet.	None	None	None	None	N
G/N	0.2009	likely_benign	0.2079	benign	-0.625	Destabilizing	0.976	D	0.516	neutral	None	None	None	None	N
G/P	0.6757	likely_pathogenic	0.6955	pathogenic	0.025	Stabilizing	0.988	D	0.682	prob.neutral	None	None	None	None	N
G/Q	0.2931	likely_benign	0.2861	benign	-0.646	Destabilizing	0.988	D	0.68	prob.neutral	None	None	None	None	N
G/R	0.3357	likely_benign	0.3222	benign	-0.649	Destabilizing	0.984	D	0.689	prob.neutral	N	0.46820191	None	None	N
G/S	0.0927	likely_benign	0.0984	benign	-0.91	Destabilizing	0.307	N	0.274	neutral	None	None	None	None	N
G/T	0.1205	likely_benign	0.1309	benign	-0.761	Destabilizing	0.851	D	0.619	neutral	None	None	None	None	N
G/V	0.1344	likely_benign	0.1446	benign	0.025	Stabilizing	0.811	D	0.653	neutral	N	0.441900743	None	None	N
G/W	0.43	ambiguous	0.4205	ambiguous	-1.123	Destabilizing	0.999	D	0.725	prob.delet.	None	None	None	None	N
G/Y	0.3818	ambiguous	0.3995	ambiguous	-0.559	Destabilizing	0.996	D	0.715	prob.delet.	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.