TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4812	14659;14660;14661	chr2:178736012;178736011;178736010	chr2:179600739;179600738;179600737
N2AB	4495	13708;13709;13710	chr2:178736012;178736011;178736010	chr2:179600739;179600738;179600737
N2A	3568	10927;10928;10929	chr2:178736012;178736011;178736010	chr2:179600739;179600738;179600737
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: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Ig-31
• Domain position: 18
• Structural Position: 28
• Q(SASA): 0.2442
• Predicted PPI site: I

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
A/D	None	None	0.864	D	0.787	0.412	0.449860987313	gnomAD-4.0.0	1.59375E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86356E-06	0	0
A/V	None	None	0.006	N	0.303	0.146	0.184867976434	gnomAD-4.0.0	1.59375E-06	None	None	None	None	I	None	0	0	None	4.77509E-05	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
A/C	0.659	likely_pathogenic	0.5968	pathogenic	-0.792	Destabilizing	0.985	D	0.67	neutral	None	None	None	None	I
A/D	0.8915	likely_pathogenic	0.9332	pathogenic	-0.806	Destabilizing	0.864	D	0.787	deleterious	D	0.674772333	None	None	I
A/E	0.7717	likely_pathogenic	0.8612	pathogenic	-0.711	Destabilizing	0.894	D	0.782	deleterious	None	None	None	None	I
A/F	0.7916	likely_pathogenic	0.7994	pathogenic	-0.596	Destabilizing	0.894	D	0.789	deleterious	None	None	None	None	I
A/G	0.259	likely_benign	0.2412	benign	-1.133	Destabilizing	0.645	D	0.626	neutral	D	0.533135016	None	None	I
A/H	0.9217	likely_pathogenic	0.9351	pathogenic	-1.144	Destabilizing	0.995	D	0.75	deleterious	None	None	None	None	I
A/I	0.4325	ambiguous	0.3877	ambiguous	0.143	Stabilizing	0.293	N	0.729	prob.delet.	None	None	None	None	I
A/K	0.8923	likely_pathogenic	0.9351	pathogenic	-0.875	Destabilizing	0.894	D	0.784	deleterious	None	None	None	None	I
A/L	0.4432	ambiguous	0.4214	ambiguous	0.143	Stabilizing	0.547	D	0.583	neutral	None	None	None	None	I
A/M	0.4885	ambiguous	0.4774	ambiguous	-0.106	Destabilizing	0.97	D	0.747	deleterious	None	None	None	None	I
A/N	0.7959	likely_pathogenic	0.8169	pathogenic	-0.87	Destabilizing	0.894	D	0.789	deleterious	None	None	None	None	I
A/P	0.8936	likely_pathogenic	0.9259	pathogenic	-0.116	Destabilizing	0.928	D	0.796	deleterious	D	0.674648421	None	None	I
A/Q	0.7665	likely_pathogenic	0.8313	pathogenic	-0.795	Destabilizing	0.945	D	0.784	deleterious	None	None	None	None	I
A/R	0.8322	likely_pathogenic	0.8886	pathogenic	-0.82	Destabilizing	0.894	D	0.791	deleterious	None	None	None	None	I
A/S	0.1862	likely_benign	0.1766	benign	-1.355	Destabilizing	0.477	N	0.594	neutral	D	0.564157242	None	None	I
A/T	0.1308	likely_benign	0.1262	benign	-1.117	Destabilizing	0.013	N	0.393	neutral	N	0.449783432	None	None	I
A/V	0.177	likely_benign	0.1638	benign	-0.116	Destabilizing	0.006	N	0.303	neutral	N	0.435641596	None	None	I
A/W	0.9716	likely_pathogenic	0.9767	pathogenic	-1.043	Destabilizing	0.995	D	0.719	prob.delet.	None	None	None	None	I
A/Y	0.912	likely_pathogenic	0.9214	pathogenic	-0.531	Destabilizing	0.945	D	0.794	deleterious	None	None	None	None	I

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.