TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7324	22195;22196;22197	chr2:178722929;178722928;178722927	chr2:179587656;179587655;179587654
N2AB	7007	21244;21245;21246	chr2:178722929;178722928;178722927	chr2:179587656;179587655;179587654
N2A	6080	18463;18464;18465	chr2:178722929;178722928;178722927	chr2:179587656;179587655;179587654
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Ig-58
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.815
• 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
Y/C	None	None	0.999	N	0.425	0.336	0.54038131941	gnomAD-4.0.0	6.85872E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.0087E-07	0	0
Y/D	rs765632650	0.335	0.984	N	0.411	0.323	0.677748964116	gnomAD-2.1.1	1.45E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	3.17E-05	0
Y/D	rs765632650	0.335	0.984	N	0.411	0.323	0.677748964116	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	4.41E-05	0	0
Y/D	rs765632650	0.335	0.984	N	0.411	0.323	0.677748964116	gnomAD-4.0.0	2.11223E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.80169E-05	0	1.60658E-05

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
Y/A	0.529	ambiguous	0.6941	pathogenic	-1.182	Destabilizing	0.828	D	0.405	neutral	None	None	None	None	N
Y/C	0.1942	likely_benign	0.2816	benign	-0.404	Destabilizing	0.999	D	0.425	neutral	N	0.513529634	None	None	N
Y/D	0.461	ambiguous	0.6613	pathogenic	0.298	Stabilizing	0.984	D	0.411	neutral	N	0.497040029	None	None	N
Y/E	0.6748	likely_pathogenic	0.8199	pathogenic	0.333	Stabilizing	0.959	D	0.431	neutral	None	None	None	None	N
Y/F	0.1008	likely_benign	0.1075	benign	-0.39	Destabilizing	0.007	N	0.215	neutral	N	0.469181424	None	None	N
Y/G	0.5689	likely_pathogenic	0.7486	pathogenic	-1.418	Destabilizing	0.921	D	0.432	neutral	None	None	None	None	N
Y/H	0.2183	likely_benign	0.2971	benign	-0.001	Destabilizing	0.991	D	0.439	neutral	N	0.470989578	None	None	N
Y/I	0.4481	ambiguous	0.5421	ambiguous	-0.525	Destabilizing	0.759	D	0.411	neutral	None	None	None	None	N
Y/K	0.6491	likely_pathogenic	0.7812	pathogenic	-0.431	Destabilizing	0.036	N	0.287	neutral	None	None	None	None	N
Y/L	0.5019	ambiguous	0.6138	pathogenic	-0.525	Destabilizing	0.311	N	0.397	neutral	None	None	None	None	N
Y/M	0.6782	likely_pathogenic	0.7749	pathogenic	-0.482	Destabilizing	0.993	D	0.407	neutral	None	None	None	None	N
Y/N	0.2941	likely_benign	0.4416	ambiguous	-0.845	Destabilizing	0.984	D	0.415	neutral	N	0.475491321	None	None	N
Y/P	0.9797	likely_pathogenic	0.9892	pathogenic	-0.73	Destabilizing	0.994	D	0.451	neutral	None	None	None	None	N
Y/Q	0.5436	ambiguous	0.7115	pathogenic	-0.721	Destabilizing	0.961	D	0.427	neutral	None	None	None	None	N
Y/R	0.4006	ambiguous	0.5444	ambiguous	-0.134	Destabilizing	0.944	D	0.41	neutral	None	None	None	None	N
Y/S	0.2282	likely_benign	0.3588	ambiguous	-1.263	Destabilizing	0.19	N	0.311	neutral	N	0.431527113	None	None	N
Y/T	0.423	ambiguous	0.5721	pathogenic	-1.136	Destabilizing	0.921	D	0.416	neutral	None	None	None	None	N
Y/V	0.3208	likely_benign	0.4016	ambiguous	-0.73	Destabilizing	0.959	D	0.421	neutral	None	None	None	None	N
Y/W	0.479	ambiguous	0.5478	ambiguous	-0.302	Destabilizing	0.999	D	0.446	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.