TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31554	94885;94886;94887	chr2:178546768;178546767;178546766	chr2:179411495;179411494;179411493
N2AB	29913	89962;89963;89964	chr2:178546768;178546767;178546766	chr2:179411495;179411494;179411493
N2A	28986	87181;87182;87183	chr2:178546768;178546767;178546766	chr2:179411495;179411494;179411493
N2B	22489	67690;67691;67692	chr2:178546768;178546767;178546766	chr2:179411495;179411494;179411493
Novex-1	22614	68065;68066;68067	chr2:178546768;178546767;178546766	chr2:179411495;179411494;179411493
Novex-2	22681	68266;68267;68268	chr2:178546768;178546767;178546766	chr2:179411495;179411494;179411493
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGT
• RefSeq wild type template codon: CCA
• Domain: Fn3-118
• Domain position: 49
• Structural Position: 63
• Q(SASA): 0.1936
• 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/S	None	None	0.956	N	0.542	0.316	0.286465849087	gnomAD-4.0.0	4.78953E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.29642E-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	0.2125	likely_benign	0.1669	benign	-0.448	Destabilizing	0.37	N	0.333	neutral	N	0.474947772	None	None	N
G/C	0.3053	likely_benign	0.2292	benign	-0.821	Destabilizing	1.0	D	0.695	prob.neutral	D	0.545433144	None	None	N
G/D	0.4131	ambiguous	0.3189	benign	-0.498	Destabilizing	0.956	D	0.58	neutral	N	0.511313261	None	None	N
G/E	0.4117	ambiguous	0.3076	benign	-0.636	Destabilizing	0.995	D	0.596	neutral	None	None	None	None	N
G/F	0.7395	likely_pathogenic	0.6384	pathogenic	-1.068	Destabilizing	0.999	D	0.703	prob.neutral	None	None	None	None	N
G/H	0.564	ambiguous	0.4635	ambiguous	-0.852	Destabilizing	0.999	D	0.661	neutral	None	None	None	None	N
G/I	0.4669	ambiguous	0.3438	ambiguous	-0.45	Destabilizing	0.998	D	0.719	prob.delet.	None	None	None	None	N
G/K	0.6198	likely_pathogenic	0.5003	ambiguous	-0.928	Destabilizing	0.995	D	0.603	neutral	None	None	None	None	N
G/L	0.6008	likely_pathogenic	0.4841	ambiguous	-0.45	Destabilizing	0.995	D	0.684	prob.neutral	None	None	None	None	N
G/M	0.614	likely_pathogenic	0.5146	ambiguous	-0.517	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
G/N	0.3517	ambiguous	0.2921	benign	-0.504	Destabilizing	0.437	N	0.305	neutral	None	None	None	None	N
G/P	0.839	likely_pathogenic	0.7313	pathogenic	-0.414	Destabilizing	0.998	D	0.69	prob.neutral	None	None	None	None	N
G/Q	0.4696	ambiguous	0.3809	ambiguous	-0.743	Destabilizing	0.998	D	0.685	prob.neutral	None	None	None	None	N
G/R	0.4617	ambiguous	0.3666	ambiguous	-0.562	Destabilizing	0.997	D	0.681	prob.neutral	N	0.497677291	None	None	N
G/S	0.1165	likely_benign	0.1012	benign	-0.679	Destabilizing	0.956	D	0.542	neutral	N	0.519177809	None	None	N
G/T	0.2315	likely_benign	0.181	benign	-0.74	Destabilizing	0.995	D	0.602	neutral	None	None	None	None	N
G/V	0.3342	likely_benign	0.24	benign	-0.414	Destabilizing	0.994	D	0.702	prob.neutral	N	0.498918285	None	None	N
G/W	0.5964	likely_pathogenic	0.4763	ambiguous	-1.268	Destabilizing	1.0	D	0.661	neutral	None	None	None	None	N
G/Y	0.6134	likely_pathogenic	0.4951	ambiguous	-0.906	Destabilizing	1.0	D	0.699	prob.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.