TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31896	95911;95912;95913	chr2:178545424;178545423;178545422	chr2:179410151;179410150;179410149
N2AB	30255	90988;90989;90990	chr2:178545424;178545423;178545422	chr2:179410151;179410150;179410149
N2A	29328	88207;88208;88209	chr2:178545424;178545423;178545422	chr2:179410151;179410150;179410149
N2B	22831	68716;68717;68718	chr2:178545424;178545423;178545422	chr2:179410151;179410150;179410149
Novex-1	22956	69091;69092;69093	chr2:178545424;178545423;178545422	chr2:179410151;179410150;179410149
Novex-2	23023	69292;69293;69294	chr2:178545424;178545423;178545422	chr2:179410151;179410150;179410149
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-120
• Domain position: 90
• Structural Position: 122
• Q(SASA): 0.6063
• 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
E/K	rs745365163	0.554	0.256	N	0.483	0.207	0.384584525793	gnomAD-2.1.1	5.12E-05	None	None	None	None	N	None	0	2.88E-05	None	0	4.63058E-04	None	1.02683E-04	None	0	8E-06	0
E/K	rs745365163	0.554	0.256	N	0.483	0.207	0.384584525793	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	0	3.861E-04	None	0	0	0	0	0
E/K	rs745365163	0.554	0.256	N	0.483	0.207	0.384584525793	gnomAD-4.0.0	1.68914E-05	None	None	None	None	N	None	0	1.68976E-05	None	0	2.24336E-04	None	0	0	3.4208E-06	1.22793E-04	1.61928E-05
E/V	rs774355988	0.003	0.303	N	0.595	0.146	0.494838880905	gnomAD-2.1.1	5.37E-05	None	None	None	None	N	None	0	0	None	0	5.6E-05	None	4.10341E-04	None	0	0	0
E/V	rs774355988	0.003	0.303	N	0.595	0.146	0.494838880905	gnomAD-4.0.0	2.00499E-05	None	None	None	None	N	None	0	0	None	0	2.53807E-05	None	0	0	0	3.30033E-04	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
E/A	0.1004	likely_benign	0.1042	benign	-0.208	Destabilizing	0.012	N	0.483	neutral	N	0.49211892	None	None	N
E/C	0.6738	likely_pathogenic	0.7062	pathogenic	-0.097	Destabilizing	0.869	D	0.66	prob.neutral	None	None	None	None	N
E/D	0.0849	likely_benign	0.0925	benign	-0.261	Destabilizing	None	N	0.192	neutral	N	0.44973358	None	None	N
E/F	0.5833	likely_pathogenic	0.5966	pathogenic	-0.076	Destabilizing	0.637	D	0.643	neutral	None	None	None	None	N
E/G	0.1388	likely_benign	0.1378	benign	-0.374	Destabilizing	None	N	0.381	neutral	D	0.522231183	None	None	N
E/H	0.3726	ambiguous	0.3858	ambiguous	0.373	Stabilizing	0.637	D	0.509	neutral	None	None	None	None	N
E/I	0.22	likely_benign	0.2354	benign	0.185	Stabilizing	0.366	N	0.647	neutral	None	None	None	None	N
E/K	0.1123	likely_benign	0.1117	benign	0.467	Stabilizing	0.256	N	0.483	neutral	N	0.52153775	None	None	N
E/L	0.2201	likely_benign	0.2346	benign	0.185	Stabilizing	0.366	N	0.634	neutral	None	None	None	None	N
E/M	0.3031	likely_benign	0.3079	benign	0.117	Stabilizing	0.869	D	0.621	neutral	None	None	None	None	N
E/N	0.1685	likely_benign	0.187	benign	0.076	Stabilizing	0.039	N	0.433	neutral	None	None	None	None	N
E/P	0.234	likely_benign	0.2711	benign	0.073	Stabilizing	0.366	N	0.585	neutral	None	None	None	None	N
E/Q	0.1324	likely_benign	0.1311	benign	0.119	Stabilizing	0.135	N	0.597	neutral	N	0.483366151	None	None	N
E/R	0.2085	likely_benign	0.2074	benign	0.703	Stabilizing	0.366	N	0.553	neutral	None	None	None	None	N
E/S	0.1453	likely_benign	0.1514	benign	-0.053	Destabilizing	0.039	N	0.459	neutral	None	None	None	None	N
E/T	0.1651	likely_benign	0.1723	benign	0.094	Stabilizing	0.075	N	0.568	neutral	None	None	None	None	N
E/V	0.1317	likely_benign	0.1396	benign	0.073	Stabilizing	0.303	N	0.595	neutral	N	0.503298706	None	None	N
E/W	0.8114	likely_pathogenic	0.811	pathogenic	0.058	Stabilizing	0.869	D	0.698	prob.delet.	None	None	None	None	N
E/Y	0.4548	ambiguous	0.4785	ambiguous	0.17	Stabilizing	0.637	D	0.618	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.