TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8492	25699;25700;25701	chr2:178717260;178717259;178717258	chr2:179581987;179581986;179581985
N2AB	8175	24748;24749;24750	chr2:178717260;178717259;178717258	chr2:179581987;179581986;179581985
N2A	7248	21967;21968;21969	chr2:178717260;178717259;178717258	chr2:179581987;179581986;179581985
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: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-70
• Domain position: 37
• Structural Position: 51
• Q(SASA): 0.6627
• 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
D/A	None	None	0.997	N	0.642	0.453	0.341226946553	gnomAD-4.0.0	6.84268E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99541E-07	0	0
D/E	rs777349143	-0.113	0.12	N	0.338	0.098	0.0611884634855	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.87E-06	0
D/E	rs777349143	-0.113	0.12	N	0.338	0.098	0.0611884634855	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	2.06868E-04	0
D/E	rs777349143	-0.113	0.12	N	0.338	0.098	0.0611884634855	gnomAD-4.0.0	5.57758E-06	None	None	None	None	N	None	1.33494E-05	0	None	0	0	None	0	1.64474E-04	4.23838E-06	2.19578E-05	0
D/G	None	None	0.993	N	0.673	0.457	0.267755039894	gnomAD-4.0.0	6.84268E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99541E-07	0	0
D/N	rs770655555	0.39	0.997	N	0.651	0.272	0.284150004643	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.87E-06	0
D/N	rs770655555	0.39	0.997	N	0.651	0.272	0.284150004643	gnomAD-4.0.0	1.36854E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99543E-07	0	1.65689E-05
D/Y	rs770655555	None	1.0	N	0.7	0.412	0.508223314113	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
D/Y	rs770655555	None	1.0	N	0.7	0.412	0.508223314113	gnomAD-4.0.0	6.57073E-06	None	None	None	None	N	None	2.41173E-05	0	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
D/A	0.6019	likely_pathogenic	0.5005	ambiguous	-0.699	Destabilizing	0.997	D	0.642	neutral	N	0.459066838	None	None	N
D/C	0.9525	likely_pathogenic	0.9149	pathogenic	-0.241	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
D/E	0.3185	likely_benign	0.2413	benign	-0.641	Destabilizing	0.12	N	0.338	neutral	N	0.502946415	None	None	N
D/F	0.9277	likely_pathogenic	0.9004	pathogenic	-0.414	Destabilizing	1.0	D	0.7	prob.neutral	None	None	None	None	N
D/G	0.3345	likely_benign	0.2674	benign	-0.991	Destabilizing	0.993	D	0.673	neutral	N	0.462999949	None	None	N
D/H	0.8427	likely_pathogenic	0.7625	pathogenic	-0.595	Destabilizing	1.0	D	0.67	neutral	N	0.510265731	None	None	N
D/I	0.9237	likely_pathogenic	0.8766	pathogenic	0.058	Stabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
D/K	0.9161	likely_pathogenic	0.8559	pathogenic	-0.304	Destabilizing	0.999	D	0.668	neutral	None	None	None	None	N
D/L	0.8611	likely_pathogenic	0.8127	pathogenic	0.058	Stabilizing	1.0	D	0.72	prob.delet.	None	None	None	None	N
D/M	0.9481	likely_pathogenic	0.9166	pathogenic	0.46	Stabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
D/N	0.2325	likely_benign	0.1946	benign	-0.691	Destabilizing	0.997	D	0.651	neutral	N	0.4694257	None	None	N
D/P	0.9913	likely_pathogenic	0.9822	pathogenic	-0.171	Destabilizing	0.995	D	0.691	prob.neutral	None	None	None	None	N
D/Q	0.818	likely_pathogenic	0.7233	pathogenic	-0.602	Destabilizing	0.998	D	0.693	prob.neutral	None	None	None	None	N
D/R	0.917	likely_pathogenic	0.8584	pathogenic	-0.11	Destabilizing	0.999	D	0.704	prob.neutral	None	None	None	None	N
D/S	0.4715	ambiguous	0.3977	ambiguous	-0.87	Destabilizing	0.992	D	0.638	neutral	None	None	None	None	N
D/T	0.841	likely_pathogenic	0.7844	pathogenic	-0.636	Destabilizing	0.997	D	0.713	prob.delet.	None	None	None	None	N
D/V	0.7942	likely_pathogenic	0.7007	pathogenic	-0.171	Destabilizing	0.998	D	0.725	prob.delet.	N	0.483033669	None	None	N
D/W	0.985	likely_pathogenic	0.9726	pathogenic	-0.201	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
D/Y	0.6597	likely_pathogenic	0.575	pathogenic	-0.178	Destabilizing	1.0	D	0.7	prob.neutral	N	0.51726717	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.