TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26420	79483;79484;79485	chr2:178566874;178566873;178566872	chr2:179431601;179431600;179431599
N2AB	24779	74560;74561;74562	chr2:178566874;178566873;178566872	chr2:179431601;179431600;179431599
N2A	23852	71779;71780;71781	chr2:178566874;178566873;178566872	chr2:179431601;179431600;179431599
N2B	17355	52288;52289;52290	chr2:178566874;178566873;178566872	chr2:179431601;179431600;179431599
Novex-1	17480	52663;52664;52665	chr2:178566874;178566873;178566872	chr2:179431601;179431600;179431599
Novex-2	17547	52864;52865;52866	chr2:178566874;178566873;178566872	chr2:179431601;179431600;179431599
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: Fn3-80
• Domain position: 35
• Structural Position: 37
• Q(SASA): 0.0942
• 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/C	None	None	1.0	D	0.804	0.557	0.66885242914	gnomAD-4.0.0	1.59187E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85907E-06	0	0
G/D	None	None	1.0	N	0.839	0.601	0.398283496042	gnomAD-4.0.0	2.40065E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	3.66327E-05

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	0.3978	ambiguous	0.373	ambiguous	-0.677	Destabilizing	1.0	D	0.596	neutral	N	0.504862405	None	None	N
G/C	0.5134	ambiguous	0.4707	ambiguous	-0.767	Destabilizing	1.0	D	0.804	deleterious	D	0.522436909	None	None	N
G/D	0.9013	likely_pathogenic	0.8876	pathogenic	-1.685	Destabilizing	1.0	D	0.839	deleterious	N	0.513015933	None	None	N
G/E	0.9399	likely_pathogenic	0.9261	pathogenic	-1.604	Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
G/F	0.944	likely_pathogenic	0.9342	pathogenic	-0.678	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
G/H	0.8878	likely_pathogenic	0.867	pathogenic	-1.594	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
G/I	0.9502	likely_pathogenic	0.9334	pathogenic	0.096	Stabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
G/K	0.9866	likely_pathogenic	0.9855	pathogenic	-1.107	Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	N
G/L	0.9395	likely_pathogenic	0.9218	pathogenic	0.096	Stabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
G/M	0.9482	likely_pathogenic	0.9326	pathogenic	-0.053	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
G/N	0.7094	likely_pathogenic	0.5672	pathogenic	-1.077	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
G/P	0.9991	likely_pathogenic	0.9983	pathogenic	-0.119	Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
G/Q	0.9217	likely_pathogenic	0.8972	pathogenic	-1.059	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
G/R	0.9493	likely_pathogenic	0.9446	pathogenic	-1.054	Destabilizing	1.0	D	0.878	deleterious	N	0.509444308	None	None	N
G/S	0.2315	likely_benign	0.197	benign	-1.363	Destabilizing	1.0	D	0.66	neutral	N	0.480539952	None	None	N
G/T	0.6724	likely_pathogenic	0.6148	pathogenic	-1.196	Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
G/V	0.8905	likely_pathogenic	0.8677	pathogenic	-0.119	Destabilizing	1.0	D	0.889	deleterious	D	0.537463291	None	None	N
G/W	0.8918	likely_pathogenic	0.8748	pathogenic	-1.348	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
G/Y	0.8836	likely_pathogenic	0.8522	pathogenic	-0.791	Destabilizing	1.0	D	0.852	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.