TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15976	48151;48152;48153	chr2:178616963;178616962;178616961	chr2:179481690;179481689;179481688
N2AB	14335	43228;43229;43230	chr2:178616963;178616962;178616961	chr2:179481690;179481689;179481688
N2A	13408	40447;40448;40449	chr2:178616963;178616962;178616961	chr2:179481690;179481689;179481688
N2B	6911	20956;20957;20958	chr2:178616963;178616962;178616961	chr2:179481690;179481689;179481688
Novex-1	7036	21331;21332;21333	chr2:178616963;178616962;178616961	chr2:179481690;179481689;179481688
Novex-2	7103	21532;21533;21534	chr2:178616963;178616962;178616961	chr2:179481690;179481689;179481688
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: Ig-109
• Domain position: 9
• Structural Position: 23
• Q(SASA): 0.335
• 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/A	rs2057447237	None	0.999	N	0.556	0.31	0.511047945453	gnomAD-4.0.0	7.96706E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.43142E-05	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	0.3799	ambiguous	0.4779	ambiguous	-1.156	Destabilizing	0.999	D	0.556	neutral	N	0.447079259	None	None	N
V/C	0.7903	likely_pathogenic	0.8145	pathogenic	-0.8	Destabilizing	1.0	D	0.673	neutral	None	None	None	None	N
V/D	0.8299	likely_pathogenic	0.8509	pathogenic	-0.846	Destabilizing	1.0	D	0.734	prob.delet.	N	0.506796605	None	None	N
V/E	0.5478	ambiguous	0.6069	pathogenic	-0.895	Destabilizing	1.0	D	0.675	prob.neutral	None	None	None	None	N
V/F	0.4414	ambiguous	0.447	ambiguous	-0.972	Destabilizing	1.0	D	0.686	prob.neutral	D	0.547477914	None	None	N
V/G	0.6684	likely_pathogenic	0.684	pathogenic	-1.409	Destabilizing	1.0	D	0.714	prob.delet.	D	0.548830686	None	None	N
V/H	0.8649	likely_pathogenic	0.8868	pathogenic	-0.882	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
V/I	0.1269	likely_benign	0.1265	benign	-0.591	Destabilizing	0.997	D	0.474	neutral	N	0.501896061	None	None	N
V/K	0.7388	likely_pathogenic	0.7782	pathogenic	-1.032	Destabilizing	1.0	D	0.675	prob.neutral	None	None	None	None	N
V/L	0.4759	ambiguous	0.5041	ambiguous	-0.591	Destabilizing	0.997	D	0.539	neutral	N	0.499180298	None	None	N
V/M	0.3904	ambiguous	0.4251	ambiguous	-0.454	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
V/N	0.6912	likely_pathogenic	0.7341	pathogenic	-0.758	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
V/P	0.8779	likely_pathogenic	0.8893	pathogenic	-0.743	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
V/Q	0.624	likely_pathogenic	0.6843	pathogenic	-0.971	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
V/R	0.6687	likely_pathogenic	0.7171	pathogenic	-0.446	Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	N
V/S	0.4682	ambiguous	0.5378	ambiguous	-1.229	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
V/T	0.442	ambiguous	0.5245	ambiguous	-1.174	Destabilizing	0.999	D	0.64	neutral	None	None	None	None	N
V/W	0.9645	likely_pathogenic	0.9658	pathogenic	-1.095	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
V/Y	0.8172	likely_pathogenic	0.8261	pathogenic	-0.829	Destabilizing	1.0	D	0.699	prob.neutral	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.