TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33569	100930;100931;100932	chr2:178536042;178536041;178536040	chr2:179400769;179400768;179400767
N2AB	31928	96007;96008;96009	chr2:178536042;178536041;178536040	chr2:179400769;179400768;179400767
N2A	31001	93226;93227;93228	chr2:178536042;178536041;178536040	chr2:179400769;179400768;179400767
N2B	24504	73735;73736;73737	chr2:178536042;178536041;178536040	chr2:179400769;179400768;179400767
Novex-1	24629	74110;74111;74112	chr2:178536042;178536041;178536040	chr2:179400769;179400768;179400767
Novex-2	24696	74311;74312;74313	chr2:178536042;178536041;178536040	chr2:179400769;179400768;179400767
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAA
• RefSeq wild type template codon: GTT
• Domain: Ig-158
• Domain position: 74
• Structural Position: 155
• Q(SASA): 0.1257
• 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/H	rs1289268364	-1.436	1.0	N	0.707	0.401	0.442054744378	gnomAD-2.1.1	8.6E-06	None	None	None	None	N	None	0	0	None	0	0	None	7.61E-05	None	0	0	0
Q/H	rs1289268364	-1.436	1.0	N	0.707	0.401	0.442054744378	gnomAD-4.0.0	3.31873E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	3.05857E-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
Q/A	0.5545	ambiguous	0.4975	ambiguous	-1.122	Destabilizing	0.999	D	0.541	neutral	None	None	None	None	N
Q/C	0.9431	likely_pathogenic	0.9149	pathogenic	-0.568	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
Q/D	0.9583	likely_pathogenic	0.9048	pathogenic	-1.187	Destabilizing	0.998	D	0.509	neutral	None	None	None	None	N
Q/E	0.3259	likely_benign	0.2082	benign	-0.977	Destabilizing	0.996	D	0.501	neutral	N	0.480838425	None	None	N
Q/F	0.9628	likely_pathogenic	0.9367	pathogenic	-0.711	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
Q/G	0.8078	likely_pathogenic	0.7516	pathogenic	-1.524	Destabilizing	0.999	D	0.607	neutral	None	None	None	None	N
Q/H	0.7253	likely_pathogenic	0.5812	pathogenic	-1.099	Destabilizing	1.0	D	0.707	prob.neutral	N	0.488352583	None	None	N
Q/I	0.7481	likely_pathogenic	0.6508	pathogenic	-0.048	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	N
Q/K	0.6113	likely_pathogenic	0.4036	ambiguous	-0.261	Destabilizing	0.998	D	0.569	neutral	N	0.477222117	None	None	N
Q/L	0.538	ambiguous	0.4137	ambiguous	-0.048	Destabilizing	0.998	D	0.607	neutral	N	0.496656027	None	None	N
Q/M	0.599	likely_pathogenic	0.5703	pathogenic	0.247	Stabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
Q/N	0.7497	likely_pathogenic	0.6646	pathogenic	-0.988	Destabilizing	1.0	D	0.627	neutral	None	None	None	None	N
Q/P	0.9944	likely_pathogenic	0.9855	pathogenic	-0.379	Destabilizing	0.999	D	0.678	prob.neutral	N	0.511318683	None	None	N
Q/R	0.6297	likely_pathogenic	0.4206	ambiguous	-0.295	Destabilizing	0.997	D	0.516	neutral	N	0.47539532	None	None	N
Q/S	0.4723	ambiguous	0.4574	ambiguous	-1.292	Destabilizing	0.999	D	0.511	neutral	None	None	None	None	N
Q/T	0.3413	ambiguous	0.2897	benign	-0.877	Destabilizing	0.996	D	0.607	neutral	None	None	None	None	N
Q/V	0.5838	likely_pathogenic	0.4913	ambiguous	-0.379	Destabilizing	0.999	D	0.658	neutral	None	None	None	None	N
Q/W	0.9782	likely_pathogenic	0.9521	pathogenic	-0.538	Destabilizing	1.0	D	0.766	deleterious	None	None	None	None	N
Q/Y	0.942	likely_pathogenic	0.8879	pathogenic	-0.244	Destabilizing	1.0	D	0.724	prob.delet.	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.