TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35654	107185;107186;107187	chr2:178528791;178528790;178528789	chr2:179393518;179393517;179393516
N2AB	34013	102262;102263;102264	chr2:178528791;178528790;178528789	chr2:179393518;179393517;179393516
N2A	33086	99481;99482;99483	chr2:178528791;178528790;178528789	chr2:179393518;179393517;179393516
N2B	26589	79990;79991;79992	chr2:178528791;178528790;178528789	chr2:179393518;179393517;179393516
Novex-1	26714	80365;80366;80367	chr2:178528791;178528790;178528789	chr2:179393518;179393517;179393516
Novex-2	26781	80566;80567;80568	chr2:178528791;178528790;178528789	chr2:179393518;179393517;179393516
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: Ig-167
• Domain position: 48
• Structural Position: 125
• Q(SASA): 0.3509
• 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	1.0	N	0.658	0.343	0.504907739247	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.2229	likely_benign	0.1948	benign	-0.451	Destabilizing	1.0	D	0.561	neutral	N	0.481627859	None	None	N
G/C	0.5307	ambiguous	0.5294	ambiguous	-0.859	Destabilizing	1.0	D	0.723	prob.delet.	N	0.483361443	None	None	N
G/D	0.5898	likely_pathogenic	0.5797	pathogenic	-0.643	Destabilizing	1.0	D	0.743	deleterious	N	0.481627859	None	None	N
G/E	0.531	ambiguous	0.5075	ambiguous	-0.782	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
G/F	0.8236	likely_pathogenic	0.8103	pathogenic	-1.079	Destabilizing	1.0	D	0.716	prob.delet.	None	None	None	None	N
G/H	0.7227	likely_pathogenic	0.6965	pathogenic	-0.814	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
G/I	0.5467	ambiguous	0.5078	ambiguous	-0.432	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
G/K	0.7396	likely_pathogenic	0.7287	pathogenic	-0.933	Destabilizing	1.0	D	0.744	deleterious	None	None	None	None	N
G/L	0.7039	likely_pathogenic	0.673	pathogenic	-0.432	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
G/M	0.7565	likely_pathogenic	0.7146	pathogenic	-0.421	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
G/N	0.6293	likely_pathogenic	0.6038	pathogenic	-0.556	Destabilizing	1.0	D	0.662	neutral	None	None	None	None	N
G/P	0.9757	likely_pathogenic	0.9841	pathogenic	-0.401	Destabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	N
G/Q	0.6217	likely_pathogenic	0.5873	pathogenic	-0.823	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
G/R	0.543	ambiguous	0.5416	ambiguous	-0.512	Destabilizing	1.0	D	0.72	prob.delet.	N	0.481627859	None	None	N
G/S	0.1684	likely_benign	0.149	benign	-0.741	Destabilizing	1.0	D	0.658	neutral	N	0.481107784	None	None	N
G/T	0.3268	likely_benign	0.2841	benign	-0.803	Destabilizing	1.0	D	0.744	deleterious	None	None	None	None	N
G/V	0.422	ambiguous	0.3858	ambiguous	-0.401	Destabilizing	1.0	D	0.747	deleterious	N	0.482147934	None	None	N
G/W	0.73	likely_pathogenic	0.7422	pathogenic	-1.277	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
G/Y	0.7849	likely_pathogenic	0.7662	pathogenic	-0.906	Destabilizing	1.0	D	0.713	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.