TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32270	97033;97034;97035	chr2:178543165;178543164;178543163	chr2:179407892;179407891;179407890
N2AB	30629	92110;92111;92112	chr2:178543165;178543164;178543163	chr2:179407892;179407891;179407890
N2A	29702	89329;89330;89331	chr2:178543165;178543164;178543163	chr2:179407892;179407891;179407890
N2B	23205	69838;69839;69840	chr2:178543165;178543164;178543163	chr2:179407892;179407891;179407890
Novex-1	23330	70213;70214;70215	chr2:178543165;178543164;178543163	chr2:179407892;179407891;179407890
Novex-2	23397	70414;70415;70416	chr2:178543165;178543164;178543163	chr2:179407892;179407891;179407890
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: Fn3-123
• Domain position: 69
• Structural Position: 100
• Q(SASA): 0.3953
• 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/D	None	None	0.523	N	0.503	0.262	0.227934060464	gnomAD-4.0.0	1.59171E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43275E-05	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	0.3151	likely_benign	0.2912	benign	-0.598	Destabilizing	0.175	N	0.425	neutral	N	0.519276596	None	None	N
G/C	0.4454	ambiguous	0.4527	ambiguous	-0.888	Destabilizing	0.035	N	0.629	neutral	D	0.525149615	None	None	N
G/D	0.2864	likely_benign	0.3017	benign	-1.225	Destabilizing	0.523	D	0.503	neutral	N	0.50753945	None	None	N
G/E	0.3694	ambiguous	0.3648	ambiguous	-1.376	Destabilizing	0.886	D	0.647	neutral	None	None	None	None	N
G/F	0.7978	likely_pathogenic	0.7861	pathogenic	-1.215	Destabilizing	0.982	D	0.729	prob.delet.	None	None	None	None	N
G/H	0.5186	ambiguous	0.4926	ambiguous	-0.91	Destabilizing	0.995	D	0.712	prob.delet.	None	None	None	None	N
G/I	0.78	likely_pathogenic	0.7649	pathogenic	-0.59	Destabilizing	0.965	D	0.727	prob.delet.	None	None	None	None	N
G/K	0.465	ambiguous	0.4544	ambiguous	-1.184	Destabilizing	0.194	N	0.491	neutral	None	None	None	None	N
G/L	0.6998	likely_pathogenic	0.6763	pathogenic	-0.59	Destabilizing	0.932	D	0.673	neutral	None	None	None	None	N
G/M	0.6889	likely_pathogenic	0.6707	pathogenic	-0.423	Destabilizing	0.998	D	0.729	prob.delet.	None	None	None	None	N
G/N	0.2821	likely_benign	0.2816	benign	-0.758	Destabilizing	0.094	N	0.225	neutral	None	None	None	None	N
G/P	0.9781	likely_pathogenic	0.9762	pathogenic	-0.557	Destabilizing	0.984	D	0.715	prob.delet.	None	None	None	None	N
G/Q	0.4415	ambiguous	0.4241	ambiguous	-1.108	Destabilizing	0.965	D	0.717	prob.delet.	None	None	None	None	N
G/R	0.3982	ambiguous	0.391	ambiguous	-0.634	Destabilizing	0.911	D	0.659	neutral	N	0.491788261	None	None	N
G/S	0.2045	likely_benign	0.1914	benign	-0.88	Destabilizing	0.506	D	0.412	neutral	N	0.505115221	None	None	N
G/T	0.395	ambiguous	0.3672	ambiguous	-0.979	Destabilizing	0.886	D	0.647	neutral	None	None	None	None	N
G/V	0.6283	likely_pathogenic	0.6073	pathogenic	-0.557	Destabilizing	0.911	D	0.685	prob.neutral	N	0.49814459	None	None	N
G/W	0.5911	likely_pathogenic	0.5929	pathogenic	-1.383	Destabilizing	0.998	D	0.769	deleterious	None	None	None	None	N
G/Y	0.6261	likely_pathogenic	0.6154	pathogenic	-1.059	Destabilizing	0.994	D	0.732	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.