TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7622	23089;23090;23091	chr2:178721155;178721154;178721153	chr2:179585882;179585881;179585880
N2AB	7305	22138;22139;22140	chr2:178721155;178721154;178721153	chr2:179585882;179585881;179585880
N2A	6378	19357;19358;19359	chr2:178721155;178721154;178721153	chr2:179585882;179585881;179585880
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: Q
• RefSeq wild type transcript codon: CAG
• RefSeq wild type template codon: GTC
• Domain: Ig-61
• Domain position: 15
• Structural Position: 23
• Q(SASA): 0.4865
• 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
Q/R	rs1234634855	None	0.021	N	0.307	0.071	0.136095386433	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
Q/R	rs1234634855	None	0.021	N	0.307	0.071	0.136095386433	gnomAD-4.0.0	2.57847E-06	None	None	None	None	N	None	1.6956E-05	1.69976E-05	None	0	0	None	0	0	0	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
Q/A	0.1634	likely_benign	0.1671	benign	-0.272	Destabilizing	0.003	N	0.141	neutral	None	None	None	None	N
Q/C	0.6156	likely_pathogenic	0.6293	pathogenic	0.259	Stabilizing	0.843	D	0.353	neutral	None	None	None	None	N
Q/D	0.3875	ambiguous	0.4073	ambiguous	-0.034	Destabilizing	0.062	N	0.266	neutral	None	None	None	None	N
Q/E	0.067	likely_benign	0.0689	benign	-0.066	Destabilizing	0.014	N	0.339	neutral	N	0.328084087	None	None	N
Q/F	0.6582	likely_pathogenic	0.6942	pathogenic	-0.483	Destabilizing	0.3	N	0.395	neutral	None	None	None	None	N
Q/G	0.2984	likely_benign	0.2946	benign	-0.462	Destabilizing	0.18	N	0.381	neutral	None	None	None	None	N
Q/H	0.2278	likely_benign	0.2369	benign	-0.447	Destabilizing	None	N	0.274	neutral	N	0.486203307	None	None	N
Q/I	0.2978	likely_benign	0.3221	benign	0.141	Stabilizing	0.042	N	0.433	neutral	None	None	None	None	N
Q/K	0.0977	likely_benign	0.1008	benign	0.099	Stabilizing	None	N	0.199	neutral	N	0.429136516	None	None	N
Q/L	0.1273	likely_benign	0.1291	benign	0.141	Stabilizing	None	N	0.157	neutral	N	0.381670643	None	None	N
Q/M	0.3301	likely_benign	0.3454	ambiguous	0.524	Stabilizing	0.235	N	0.275	neutral	None	None	None	None	N
Q/N	0.3298	likely_benign	0.3445	ambiguous	-0.185	Destabilizing	0.032	N	0.315	neutral	None	None	None	None	N
Q/P	0.13	likely_benign	0.126	benign	0.031	Stabilizing	0.261	N	0.344	neutral	N	0.40910796	None	None	N
Q/R	0.1093	likely_benign	0.1105	benign	0.241	Stabilizing	0.021	N	0.307	neutral	N	0.436217204	None	None	N
Q/S	0.2601	likely_benign	0.2683	benign	-0.202	Destabilizing	0.043	N	0.29	neutral	None	None	None	None	N
Q/T	0.2183	likely_benign	0.2288	benign	-0.079	Destabilizing	0.008	N	0.363	neutral	None	None	None	None	N
Q/V	0.2008	likely_benign	0.2145	benign	0.031	Stabilizing	0.013	N	0.383	neutral	None	None	None	None	N
Q/W	0.5123	ambiguous	0.5261	ambiguous	-0.437	Destabilizing	0.964	D	0.369	neutral	None	None	None	None	N
Q/Y	0.4241	ambiguous	0.4465	ambiguous	-0.185	Destabilizing	0.177	N	0.341	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.