TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24650	74173;74174;74175	chr2:178572184;178572183;178572182	chr2:179436911;179436910;179436909
N2AB	23009	69250;69251;69252	chr2:178572184;178572183;178572182	chr2:179436911;179436910;179436909
N2A	22082	66469;66470;66471	chr2:178572184;178572183;178572182	chr2:179436911;179436910;179436909
N2B	15585	46978;46979;46980	chr2:178572184;178572183;178572182	chr2:179436911;179436910;179436909
Novex-1	15710	47353;47354;47355	chr2:178572184;178572183;178572182	chr2:179436911;179436910;179436909
Novex-2	15777	47554;47555;47556	chr2:178572184;178572183;178572182	chr2:179436911;179436910;179436909
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Fn3-67
• Domain position: 35
• Structural Position: 37
• Q(SASA): 0.1172
• 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	0.998	N	0.824	0.539	0.468586609112	gnomAD-4.0.0	3.18425E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71873E-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	0.2287	likely_benign	0.1937	benign	-0.587	Destabilizing	0.204	N	0.439	neutral	N	0.473591419	None	None	N
G/C	0.3242	likely_benign	0.3011	benign	-0.75	Destabilizing	1.0	D	0.919	deleterious	N	0.496268031	None	None	N
G/D	0.763	likely_pathogenic	0.7292	pathogenic	-1.3	Destabilizing	0.998	D	0.824	deleterious	N	0.492936669	None	None	N
G/E	0.7699	likely_pathogenic	0.7478	pathogenic	-1.258	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
G/F	0.8729	likely_pathogenic	0.8612	pathogenic	-0.661	Destabilizing	1.0	D	0.923	deleterious	None	None	None	None	N
G/H	0.6974	likely_pathogenic	0.6646	pathogenic	-1.435	Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
G/I	0.85	likely_pathogenic	0.8436	pathogenic	0.094	Stabilizing	1.0	D	0.919	deleterious	None	None	None	None	N
G/K	0.8895	likely_pathogenic	0.8733	pathogenic	-1.028	Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
G/L	0.7915	likely_pathogenic	0.7689	pathogenic	0.094	Stabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
G/M	0.8226	likely_pathogenic	0.8084	pathogenic	-0.055	Destabilizing	1.0	D	0.915	deleterious	None	None	None	None	N
G/N	0.5501	ambiguous	0.5327	ambiguous	-0.896	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
G/P	0.998	likely_pathogenic	0.9975	pathogenic	-0.09	Destabilizing	0.999	D	0.899	deleterious	None	None	None	None	N
G/Q	0.7108	likely_pathogenic	0.6844	pathogenic	-0.923	Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
G/R	0.794	likely_pathogenic	0.7603	pathogenic	-0.957	Destabilizing	0.999	D	0.907	deleterious	N	0.494631735	None	None	N
G/S	0.1585	likely_benign	0.1441	benign	-1.206	Destabilizing	0.718	D	0.433	neutral	N	0.471981577	None	None	N
G/T	0.4836	ambiguous	0.4564	ambiguous	-1.074	Destabilizing	0.999	D	0.828	deleterious	None	None	None	None	N
G/V	0.7286	likely_pathogenic	0.7088	pathogenic	-0.09	Destabilizing	0.999	D	0.887	deleterious	D	0.540754973	None	None	N
G/W	0.8181	likely_pathogenic	0.7763	pathogenic	-1.244	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
G/Y	0.7332	likely_pathogenic	0.7139	pathogenic	-0.709	Destabilizing	1.0	D	0.921	deleterious	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.