TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31652	95179;95180;95181	chr2:178546377;178546376;178546375	chr2:179411104;179411103;179411102
N2AB	30011	90256;90257;90258	chr2:178546377;178546376;178546375	chr2:179411104;179411103;179411102
N2A	29084	87475;87476;87477	chr2:178546377;178546376;178546375	chr2:179411104;179411103;179411102
N2B	22587	67984;67985;67986	chr2:178546377;178546376;178546375	chr2:179411104;179411103;179411102
Novex-1	22712	68359;68360;68361	chr2:178546377;178546376;178546375	chr2:179411104;179411103;179411102
Novex-2	22779	68560;68561;68562	chr2:178546377;178546376;178546375	chr2:179411104;179411103;179411102
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: Ig-152
• Domain position: 32
• Structural Position: 51
• Q(SASA): 0.2713
• 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	None	None	1.0	N	0.649	0.51	0.298403945805	gnomAD-4.0.0	1.59128E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85842E-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
G/A	0.191	likely_benign	0.1929	benign	-0.368	Destabilizing	1.0	D	0.563	neutral	N	0.448514497	None	None	N
G/C	0.3185	likely_benign	0.3202	benign	-0.829	Destabilizing	1.0	D	0.641	neutral	None	None	None	None	N
G/D	0.1415	likely_benign	0.1364	benign	-0.549	Destabilizing	1.0	D	0.655	neutral	None	None	None	None	N
G/E	0.2277	likely_benign	0.2157	benign	-0.7	Destabilizing	1.0	D	0.664	neutral	N	0.423232051	None	None	N
G/F	0.7728	likely_pathogenic	0.7742	pathogenic	-1.059	Destabilizing	1.0	D	0.619	neutral	None	None	None	None	N
G/H	0.55	ambiguous	0.5583	ambiguous	-0.745	Destabilizing	1.0	D	0.629	neutral	None	None	None	None	N
G/I	0.6553	likely_pathogenic	0.6609	pathogenic	-0.403	Destabilizing	1.0	D	0.629	neutral	None	None	None	None	N
G/K	0.6138	likely_pathogenic	0.6066	pathogenic	-0.833	Destabilizing	1.0	D	0.665	neutral	None	None	None	None	N
G/L	0.6087	likely_pathogenic	0.6161	pathogenic	-0.403	Destabilizing	1.0	D	0.657	neutral	None	None	None	None	N
G/M	0.6297	likely_pathogenic	0.6315	pathogenic	-0.361	Destabilizing	1.0	D	0.635	neutral	None	None	None	None	N
G/N	0.196	likely_benign	0.2029	benign	-0.439	Destabilizing	1.0	D	0.603	neutral	None	None	None	None	N
G/P	0.971	likely_pathogenic	0.9734	pathogenic	-0.355	Destabilizing	1.0	D	0.652	neutral	None	None	None	None	N
G/Q	0.4401	ambiguous	0.4352	ambiguous	-0.725	Destabilizing	1.0	D	0.655	neutral	None	None	None	None	N
G/R	0.5201	ambiguous	0.5092	ambiguous	-0.43	Destabilizing	1.0	D	0.649	neutral	N	0.462163802	None	None	N
G/S	0.1531	likely_benign	0.1533	benign	-0.624	Destabilizing	1.0	D	0.601	neutral	None	None	None	None	N
G/T	0.3723	ambiguous	0.384	ambiguous	-0.702	Destabilizing	1.0	D	0.664	neutral	None	None	None	None	N
G/V	0.4724	ambiguous	0.4718	ambiguous	-0.355	Destabilizing	1.0	D	0.663	neutral	N	0.469140486	None	None	N
G/W	0.5715	likely_pathogenic	0.5754	pathogenic	-1.242	Destabilizing	1.0	D	0.636	neutral	None	None	None	None	N
G/Y	0.5341	ambiguous	0.5369	ambiguous	-0.871	Destabilizing	1.0	D	0.618	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.