TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5849	17770;17771;17772	chr2:178731120;178731119;178731118	chr2:179595847;179595846;179595845
N2AB	5532	16819;16820;16821	chr2:178731120;178731119;178731118	chr2:179595847;179595846;179595845
N2A	4605	14038;14039;14040	chr2:178731120;178731119;178731118	chr2:179595847;179595846;179595845
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: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-42
• Domain position: 27
• Structural Position: 41
• Q(SASA): 0.7318
• 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
T/I	None	None	1.0	N	0.761	0.427	0.648752727461	gnomAD-4.0.0	1.59141E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43275E-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
T/A	0.2618	likely_benign	0.314	benign	-0.331	Destabilizing	0.999	D	0.58	neutral	D	0.529787166	None	None	N
T/C	0.8709	likely_pathogenic	0.8877	pathogenic	-0.238	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
T/D	0.6721	likely_pathogenic	0.6853	pathogenic	0.133	Stabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
T/E	0.6468	likely_pathogenic	0.6954	pathogenic	0.065	Stabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
T/F	0.7646	likely_pathogenic	0.7979	pathogenic	-0.748	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
T/G	0.4488	ambiguous	0.4648	ambiguous	-0.478	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
T/H	0.6727	likely_pathogenic	0.7032	pathogenic	-0.72	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
T/I	0.7975	likely_pathogenic	0.8337	pathogenic	-0.059	Destabilizing	1.0	D	0.761	deleterious	N	0.516628654	None	None	N
T/K	0.5889	likely_pathogenic	0.6337	pathogenic	-0.416	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
T/L	0.4828	ambiguous	0.5461	ambiguous	-0.059	Destabilizing	0.999	D	0.691	prob.neutral	None	None	None	None	N
T/M	0.2921	likely_benign	0.343	ambiguous	0.028	Stabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
T/N	0.3124	likely_benign	0.324	benign	-0.147	Destabilizing	1.0	D	0.804	deleterious	N	0.493154362	None	None	N
T/P	0.4325	ambiguous	0.4924	ambiguous	-0.12	Destabilizing	1.0	D	0.763	deleterious	N	0.501888162	None	None	N
T/Q	0.5351	ambiguous	0.5711	pathogenic	-0.358	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
T/R	0.5063	ambiguous	0.5694	pathogenic	-0.131	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
T/S	0.1672	likely_benign	0.1643	benign	-0.358	Destabilizing	0.999	D	0.613	neutral	N	0.485977673	None	None	N
T/V	0.6522	likely_pathogenic	0.6983	pathogenic	-0.12	Destabilizing	0.999	D	0.689	prob.neutral	None	None	None	None	N
T/W	0.8933	likely_pathogenic	0.9012	pathogenic	-0.767	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
T/Y	0.7659	likely_pathogenic	0.7944	pathogenic	-0.489	Destabilizing	1.0	D	0.81	deleterious	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.