TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18886	56881;56882;56883	chr2:178599054;178599053;178599052	chr2:179463781;179463780;179463779
N2AB	17245	51958;51959;51960	chr2:178599054;178599053;178599052	chr2:179463781;179463780;179463779
N2A	16318	49177;49178;49179	chr2:178599054;178599053;178599052	chr2:179463781;179463780;179463779
N2B	9821	29686;29687;29688	chr2:178599054;178599053;178599052	chr2:179463781;179463780;179463779
Novex-1	9946	30061;30062;30063	chr2:178599054;178599053;178599052	chr2:179463781;179463780;179463779
Novex-2	10013	30262;30263;30264	chr2:178599054;178599053;178599052	chr2:179463781;179463780;179463779
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Fn3-25
• Domain position: 3
• Structural Position: 3
• Q(SASA): 0.2827
• Predicted PPI site: I

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/E	rs1421176024	-1.682	1.0	N	0.823	0.487	0.458374381611	gnomAD-2.1.1	3.19E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	6.5E-05	0
G/R	None	None	1.0	N	0.808	0.444	0.598795731184	gnomAD-4.0.0	7.16025E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.22581E-07	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	0.2088	likely_benign	0.2588	benign	-0.806	Destabilizing	1.0	D	0.631	neutral	N	0.492066706	None	None	I
G/C	0.4583	ambiguous	0.5826	pathogenic	-0.994	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	I
G/D	0.3858	ambiguous	0.4756	ambiguous	-1.606	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	I
G/E	0.4972	ambiguous	0.6563	pathogenic	-1.657	Destabilizing	1.0	D	0.823	deleterious	N	0.485710377	None	None	I
G/F	0.8699	likely_pathogenic	0.9285	pathogenic	-1.091	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	I
G/H	0.7524	likely_pathogenic	0.8414	pathogenic	-1.463	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	I
G/I	0.8014	likely_pathogenic	0.8995	pathogenic	-0.411	Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	I
G/K	0.7872	likely_pathogenic	0.884	pathogenic	-1.336	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	I
G/L	0.72	likely_pathogenic	0.8334	pathogenic	-0.411	Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	I
G/M	0.7769	likely_pathogenic	0.8696	pathogenic	-0.375	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	I
G/N	0.5944	likely_pathogenic	0.6895	pathogenic	-1.029	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	I
G/P	0.9793	likely_pathogenic	0.9898	pathogenic	-0.503	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	I
G/Q	0.6438	likely_pathogenic	0.7598	pathogenic	-1.231	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	I
G/R	0.6788	likely_pathogenic	0.8112	pathogenic	-1.039	Destabilizing	1.0	D	0.808	deleterious	N	0.508222404	None	None	I
G/S	0.1458	likely_benign	0.1766	benign	-1.233	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	I
G/T	0.3928	ambiguous	0.5034	ambiguous	-1.22	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	I
G/V	0.643	likely_pathogenic	0.793	pathogenic	-0.503	Destabilizing	1.0	D	0.818	deleterious	N	0.520085689	None	None	I
G/W	0.809	likely_pathogenic	0.8977	pathogenic	-1.468	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	I
G/Y	0.7741	likely_pathogenic	0.86	pathogenic	-1.067	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	I

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.