TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2850	8773;8774;8775	chr2:178770153;178770152;178770151	chr2:179634880;179634879;179634878
N2AB	2850	8773;8774;8775	chr2:178770153;178770152;178770151	chr2:179634880;179634879;179634878
N2A	2850	8773;8774;8775	chr2:178770153;178770152;178770151	chr2:179634880;179634879;179634878
N2B	2804	8635;8636;8637	chr2:178770153;178770152;178770151	chr2:179634880;179634879;179634878
Novex-1	2804	8635;8636;8637	chr2:178770153;178770152;178770151	chr2:179634880;179634879;179634878
Novex-2	2804	8635;8636;8637	chr2:178770153;178770152;178770151	chr2:179634880;179634879;179634878
Novex-3	2850	8773;8774;8775	chr2:178770153;178770152;178770151	chr2:179634880;179634879;179634878

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-18
• Domain position: 56
• Structural Position: 137
• Q(SASA): 0.2148
• 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
K/R	rs1396734796	-1.068	0.999	N	0.625	0.331	0.341934017632	gnomAD-2.1.1	3.98E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
K/R	rs1396734796	-1.068	0.999	N	0.625	0.331	0.341934017632	gnomAD-4.0.0	1.59045E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43271E-05	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
K/A	0.9349	likely_pathogenic	0.9329	pathogenic	-0.786	Destabilizing	0.999	D	0.698	prob.neutral	None	None	None	None	N
K/C	0.941	likely_pathogenic	0.9431	pathogenic	-0.966	Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
K/D	0.9891	likely_pathogenic	0.9865	pathogenic	-1.179	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
K/E	0.8534	likely_pathogenic	0.8409	pathogenic	-0.997	Destabilizing	0.999	D	0.631	neutral	D	0.56120684	None	None	N
K/F	0.9859	likely_pathogenic	0.9811	pathogenic	-0.105	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
K/G	0.9662	likely_pathogenic	0.9632	pathogenic	-1.229	Destabilizing	1.0	D	0.76	deleterious	None	None	None	None	N
K/H	0.6552	likely_pathogenic	0.6566	pathogenic	-1.608	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
K/I	0.8381	likely_pathogenic	0.8066	pathogenic	0.411	Stabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
K/L	0.8652	likely_pathogenic	0.8298	pathogenic	0.411	Stabilizing	1.0	D	0.76	deleterious	None	None	None	None	N
K/M	0.731	likely_pathogenic	0.6892	pathogenic	0.222	Stabilizing	1.0	D	0.774	deleterious	D	0.549057148	None	None	N
K/N	0.9454	likely_pathogenic	0.9401	pathogenic	-1.341	Destabilizing	1.0	D	0.751	deleterious	N	0.513654969	None	None	N
K/P	0.9984	likely_pathogenic	0.9974	pathogenic	0.04	Stabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
K/Q	0.4323	ambiguous	0.4544	ambiguous	-1.211	Destabilizing	1.0	D	0.741	deleterious	N	0.511180986	None	None	N
K/R	0.1228	likely_benign	0.1367	benign	-1.286	Destabilizing	0.999	D	0.625	neutral	N	0.493088865	None	None	N
K/S	0.9225	likely_pathogenic	0.9203	pathogenic	-1.817	Destabilizing	0.999	D	0.673	neutral	None	None	None	None	N
K/T	0.617	likely_pathogenic	0.603	pathogenic	-1.418	Destabilizing	1.0	D	0.765	deleterious	N	0.493746497	None	None	N
K/V	0.8035	likely_pathogenic	0.7795	pathogenic	0.04	Stabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
K/W	0.974	likely_pathogenic	0.9687	pathogenic	-0.148	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
K/Y	0.9421	likely_pathogenic	0.9289	pathogenic	0.166	Stabilizing	1.0	D	0.819	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.