TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23114	69565;69566;69567	chr2:178576995;178576994;178576993	chr2:179441722;179441721;179441720
N2AB	21473	64642;64643;64644	chr2:178576995;178576994;178576993	chr2:179441722;179441721;179441720
N2A	20546	61861;61862;61863	chr2:178576995;178576994;178576993	chr2:179441722;179441721;179441720
N2B	14049	42370;42371;42372	chr2:178576995;178576994;178576993	chr2:179441722;179441721;179441720
Novex-1	14174	42745;42746;42747	chr2:178576995;178576994;178576993	chr2:179441722;179441721;179441720
Novex-2	14241	42946;42947;42948	chr2:178576995;178576994;178576993	chr2:179441722;179441721;179441720
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Fn3-55
• Domain position: 75
• Structural Position: 108
• Q(SASA): 0.085
• 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
V/D	None	None	0.983	D	0.901	0.842	0.924821572837	gnomAD-4.0.0	1.36863E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79922E-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
V/A	0.8355	likely_pathogenic	0.8082	pathogenic	-2.686	Highly Destabilizing	0.099	N	0.348	neutral	D	0.564823251	None	None	N
V/C	0.9543	likely_pathogenic	0.9432	pathogenic	-2.143	Highly Destabilizing	0.999	D	0.755	deleterious	None	None	None	None	N
V/D	0.9975	likely_pathogenic	0.9982	pathogenic	-3.553	Highly Destabilizing	0.983	D	0.901	deleterious	D	0.657575589	None	None	N
V/E	0.9936	likely_pathogenic	0.9945	pathogenic	-3.254	Highly Destabilizing	0.987	D	0.848	deleterious	None	None	None	None	N
V/F	0.8781	likely_pathogenic	0.8367	pathogenic	-1.466	Destabilizing	0.967	D	0.749	deleterious	D	0.587535862	None	None	N
V/G	0.9156	likely_pathogenic	0.9146	pathogenic	-3.263	Highly Destabilizing	0.967	D	0.834	deleterious	D	0.657575589	None	None	N
V/H	0.9978	likely_pathogenic	0.9979	pathogenic	-2.979	Highly Destabilizing	0.999	D	0.882	deleterious	None	None	None	None	N
V/I	0.0816	likely_benign	0.0762	benign	-1.0	Destabilizing	0.025	N	0.295	neutral	N	0.521807974	None	None	N
V/K	0.9945	likely_pathogenic	0.9953	pathogenic	-2.181	Highly Destabilizing	0.987	D	0.854	deleterious	None	None	None	None	N
V/L	0.6311	likely_pathogenic	0.5518	ambiguous	-1.0	Destabilizing	0.369	N	0.551	neutral	D	0.533446453	None	None	N
V/M	0.7511	likely_pathogenic	0.6902	pathogenic	-1.277	Destabilizing	0.975	D	0.671	neutral	None	None	None	None	N
V/N	0.9911	likely_pathogenic	0.9918	pathogenic	-2.789	Highly Destabilizing	0.996	D	0.912	deleterious	None	None	None	None	N
V/P	0.9935	likely_pathogenic	0.9923	pathogenic	-1.546	Destabilizing	0.987	D	0.872	deleterious	None	None	None	None	N
V/Q	0.9925	likely_pathogenic	0.9928	pathogenic	-2.479	Highly Destabilizing	0.996	D	0.896	deleterious	None	None	None	None	N
V/R	0.9893	likely_pathogenic	0.9908	pathogenic	-2.118	Highly Destabilizing	0.987	D	0.909	deleterious	None	None	None	None	N
V/S	0.9658	likely_pathogenic	0.9633	pathogenic	-3.319	Highly Destabilizing	0.95	D	0.805	deleterious	None	None	None	None	N
V/T	0.9148	likely_pathogenic	0.901	pathogenic	-2.876	Highly Destabilizing	0.916	D	0.606	neutral	None	None	None	None	N
V/W	0.9983	likely_pathogenic	0.9978	pathogenic	-2.02	Highly Destabilizing	0.999	D	0.852	deleterious	None	None	None	None	N
V/Y	0.989	likely_pathogenic	0.987	pathogenic	-1.774	Destabilizing	0.987	D	0.751	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.