TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6970	21133;21134;21135	chr2:178724467;178724466;178724465	chr2:179589194;179589193;179589192
N2AB	6653	20182;20183;20184	chr2:178724467;178724466;178724465	chr2:179589194;179589193;179589192
N2A	5726	17401;17402;17403	chr2:178724467;178724466;178724465	chr2:179589194;179589193;179589192
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: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-54
• Domain position: 23
• Structural Position: 34
• Q(SASA): 0.5825
• 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	rs2154303625	None	0.549	N	0.535	0.139	0.149567049428	gnomAD-4.0.0	1.59249E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86044E-06	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
K/A	0.2473	likely_benign	0.2779	benign	-0.556	Destabilizing	0.4	N	0.499	neutral	None	None	None	None	N
K/C	0.6703	likely_pathogenic	0.7022	pathogenic	-0.727	Destabilizing	0.992	D	0.56	neutral	None	None	None	None	N
K/D	0.6021	likely_pathogenic	0.6284	pathogenic	-0.229	Destabilizing	0.617	D	0.579	neutral	None	None	None	None	N
K/E	0.1379	likely_benign	0.1473	benign	-0.093	Destabilizing	0.549	D	0.515	neutral	N	0.464236964	None	None	N
K/F	0.7001	likely_pathogenic	0.7189	pathogenic	-0.099	Destabilizing	0.85	D	0.57	neutral	None	None	None	None	N
K/G	0.4843	ambiguous	0.5204	ambiguous	-0.946	Destabilizing	0.617	D	0.527	neutral	None	None	None	None	N
K/H	0.292	likely_benign	0.3052	benign	-1.221	Destabilizing	0.92	D	0.571	neutral	None	None	None	None	N
K/I	0.2219	likely_benign	0.2363	benign	0.466	Stabilizing	0.012	N	0.436	neutral	None	None	None	None	N
K/L	0.2495	likely_benign	0.2638	benign	0.466	Stabilizing	0.25	N	0.507	neutral	None	None	None	None	N
K/M	0.1585	likely_benign	0.1653	benign	0.174	Stabilizing	0.81	D	0.574	neutral	N	0.515687292	None	None	N
K/N	0.3898	ambiguous	0.3976	ambiguous	-0.698	Destabilizing	0.549	D	0.535	neutral	N	0.506489018	None	None	N
K/P	0.835	likely_pathogenic	0.8449	pathogenic	0.156	Stabilizing	0.92	D	0.596	neutral	None	None	None	None	N
K/Q	0.1215	likely_benign	0.1241	benign	-0.687	Destabilizing	0.81	D	0.55	neutral	N	0.476166111	None	None	N
K/R	0.0761	likely_benign	0.0775	benign	-0.744	Destabilizing	0.002	N	0.179	neutral	N	0.464122321	None	None	N
K/S	0.3332	likely_benign	0.3615	ambiguous	-1.314	Destabilizing	0.447	N	0.523	neutral	None	None	None	None	N
K/T	0.0966	likely_benign	0.1063	benign	-0.967	Destabilizing	0.016	N	0.276	neutral	N	0.450171589	None	None	N
K/V	0.1964	likely_benign	0.2095	benign	0.156	Stabilizing	0.25	N	0.508	neutral	None	None	None	None	N
K/W	0.7495	likely_pathogenic	0.7566	pathogenic	-0.011	Destabilizing	0.992	D	0.596	neutral	None	None	None	None	N
K/Y	0.5853	likely_pathogenic	0.6099	pathogenic	0.279	Stabilizing	0.972	D	0.561	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.