TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2701	8326;8327;8328	chr2:178771226;178771225;178771224	chr2:179635953;179635952;179635951
N2AB	2701	8326;8327;8328	chr2:178771226;178771225;178771224	chr2:179635953;179635952;179635951
N2A	2701	8326;8327;8328	chr2:178771226;178771225;178771224	chr2:179635953;179635952;179635951
N2B	2655	8188;8189;8190	chr2:178771226;178771225;178771224	chr2:179635953;179635952;179635951
Novex-1	2655	8188;8189;8190	chr2:178771226;178771225;178771224	chr2:179635953;179635952;179635951
Novex-2	2655	8188;8189;8190	chr2:178771226;178771225;178771224	chr2:179635953;179635952;179635951
Novex-3	2701	8326;8327;8328	chr2:178771226;178771225;178771224	chr2:179635953;179635952;179635951

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-16
• Domain position: 81
• Structural Position: 173
• Q(SASA): 0.6422
• 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/N	rs750526009	0.044	0.002	N	0.147	0.065	0.154104182512	gnomAD-2.1.1	3.98E-06	None	None	None	None	N	None	0	2.89E-05	None	0	0	None	0	None	0	0	0
K/N	rs750526009	0.044	0.002	N	0.147	0.065	0.154104182512	gnomAD-4.0.0	1.59076E-06	None	None	None	None	N	None	0	2.28666E-05	None	0	0	None	0	0	0	0	0
K/T	rs556548772	-0.2	0.549	N	0.511	0.138	0.286465849087	1000 genomes	1.99681E-04	None	None	None	None	N	None	8E-04	0	None	None	0	0	None	None	None	0	None

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	0.2629	likely_benign	0.2549	benign	-0.338	Destabilizing	0.617	D	0.517	neutral	None	None	None	None	N
K/C	0.646	likely_pathogenic	0.6436	pathogenic	-0.383	Destabilizing	0.992	D	0.525	neutral	None	None	None	None	N
K/D	0.4878	ambiguous	0.4686	ambiguous	0.034	Stabilizing	0.447	N	0.516	neutral	None	None	None	None	N
K/E	0.1589	likely_benign	0.1471	benign	0.089	Stabilizing	0.334	N	0.531	neutral	N	0.473591692	None	None	N
K/F	0.5582	ambiguous	0.5612	ambiguous	-0.269	Destabilizing	0.92	D	0.522	neutral	None	None	None	None	N
K/G	0.4226	ambiguous	0.412	ambiguous	-0.639	Destabilizing	0.447	N	0.513	neutral	None	None	None	None	N
K/H	0.2347	likely_benign	0.2325	benign	-0.994	Destabilizing	0.012	N	0.292	neutral	None	None	None	None	N
K/I	0.2066	likely_benign	0.2074	benign	0.406	Stabilizing	0.896	D	0.531	neutral	N	0.515332351	None	None	N
K/L	0.2486	likely_benign	0.2405	benign	0.406	Stabilizing	0.617	D	0.521	neutral	None	None	None	None	N
K/M	0.1617	likely_benign	0.1512	benign	0.319	Stabilizing	0.992	D	0.49	neutral	None	None	None	None	N
K/N	0.2284	likely_benign	0.2318	benign	-0.094	Destabilizing	0.002	N	0.147	neutral	N	0.452704411	None	None	N
K/P	0.7664	likely_pathogenic	0.7499	pathogenic	0.188	Stabilizing	0.972	D	0.551	neutral	None	None	None	None	N
K/Q	0.1137	likely_benign	0.1104	benign	-0.269	Destabilizing	0.549	D	0.53	neutral	N	0.505261399	None	None	N
K/R	0.082	likely_benign	0.0819	benign	-0.323	Destabilizing	0.004	N	0.185	neutral	N	0.46483921	None	None	N
K/S	0.2748	likely_benign	0.2742	benign	-0.722	Destabilizing	0.25	N	0.511	neutral	None	None	None	None	N
K/T	0.1145	likely_benign	0.1098	benign	-0.483	Destabilizing	0.549	D	0.511	neutral	N	0.48427037	None	None	N
K/V	0.2042	likely_benign	0.2027	benign	0.188	Stabilizing	0.92	D	0.514	neutral	None	None	None	None	N
K/W	0.6678	likely_pathogenic	0.6621	pathogenic	-0.155	Destabilizing	0.992	D	0.584	neutral	None	None	None	None	N
K/Y	0.4546	ambiguous	0.463	ambiguous	0.158	Stabilizing	0.85	D	0.516	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.