TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24244	72955;72956;72957	chr2:178573402;178573401;178573400	chr2:179438129;179438128;179438127
N2AB	22603	68032;68033;68034	chr2:178573402;178573401;178573400	chr2:179438129;179438128;179438127
N2A	21676	65251;65252;65253	chr2:178573402;178573401;178573400	chr2:179438129;179438128;179438127
N2B	15179	45760;45761;45762	chr2:178573402;178573401;178573400	chr2:179438129;179438128;179438127
Novex-1	15304	46135;46136;46137	chr2:178573402;178573401;178573400	chr2:179438129;179438128;179438127
Novex-2	15371	46336;46337;46338	chr2:178573402;178573401;178573400	chr2:179438129;179438128;179438127
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: Fn3-64
• Domain position: 23
• Structural Position: 25
• Q(SASA): 0.1845
• 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	rs1708937897	None	0.317	N	0.572	0.18	0.430126000877	gnomAD-4.0.0	7.2976E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.35069E-07	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	0.1064	likely_benign	0.1118	benign	-0.639	Destabilizing	0.027	N	0.455	neutral	N	0.388013117	None	None	N
G/C	0.1606	likely_benign	0.17	benign	-0.676	Destabilizing	0.935	D	0.633	neutral	None	None	None	None	N
G/D	0.1792	likely_benign	0.2086	benign	-2.272	Highly Destabilizing	0.001	N	0.359	neutral	None	None	None	None	N
G/E	0.1505	likely_benign	0.1806	benign	-2.107	Highly Destabilizing	0.002	N	0.373	neutral	N	0.369328569	None	None	N
G/F	0.5253	ambiguous	0.5402	ambiguous	-0.691	Destabilizing	0.555	D	0.623	neutral	None	None	None	None	N
G/H	0.3498	ambiguous	0.3834	ambiguous	-1.89	Destabilizing	0.824	D	0.571	neutral	None	None	None	None	N
G/I	0.2588	likely_benign	0.2858	benign	0.373	Stabilizing	0.38	N	0.62	neutral	None	None	None	None	N
G/K	0.3594	ambiguous	0.4104	ambiguous	-1.228	Destabilizing	0.149	N	0.534	neutral	None	None	None	None	N
G/L	0.3169	likely_benign	0.3417	ambiguous	0.373	Stabilizing	0.235	N	0.586	neutral	None	None	None	None	N
G/M	0.3756	ambiguous	0.4066	ambiguous	0.28	Stabilizing	0.935	D	0.607	neutral	None	None	None	None	N
G/N	0.1963	likely_benign	0.2221	benign	-1.37	Destabilizing	0.081	N	0.534	neutral	None	None	None	None	N
G/P	0.7839	likely_pathogenic	0.7775	pathogenic	0.078	Stabilizing	0.555	D	0.568	neutral	None	None	None	None	N
G/Q	0.2539	likely_benign	0.2844	benign	-1.243	Destabilizing	0.38	N	0.571	neutral	None	None	None	None	N
G/R	0.2901	likely_benign	0.3317	benign	-1.297	Destabilizing	0.317	N	0.572	neutral	N	0.423664486	None	None	N
G/S	0.0828	likely_benign	0.0902	benign	-1.608	Destabilizing	0.002	N	0.391	neutral	None	None	None	None	N
G/T	0.1303	likely_benign	0.1474	benign	-1.341	Destabilizing	0.001	N	0.403	neutral	None	None	None	None	N
G/V	0.1757	likely_benign	0.1914	benign	0.078	Stabilizing	0.188	N	0.587	neutral	N	0.431361249	None	None	N
G/W	0.4138	ambiguous	0.4371	ambiguous	-1.569	Destabilizing	0.935	D	0.634	neutral	None	None	None	None	N
G/Y	0.3678	ambiguous	0.3852	ambiguous	-0.892	Destabilizing	0.791	D	0.621	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.