TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20422	61489;61490;61491	chr2:178590461;178590460;178590459	chr2:179455188;179455187;179455186
N2AB	18781	56566;56567;56568	chr2:178590461;178590460;178590459	chr2:179455188;179455187;179455186
N2A	17854	53785;53786;53787	chr2:178590461;178590460;178590459	chr2:179455188;179455187;179455186
N2B	11357	34294;34295;34296	chr2:178590461;178590460;178590459	chr2:179455188;179455187;179455186
Novex-1	11482	34669;34670;34671	chr2:178590461;178590460;178590459	chr2:179455188;179455187;179455186
Novex-2	11549	34870;34871;34872	chr2:178590461;178590460;178590459	chr2:179455188;179455187;179455186
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-36
• Domain position: 52
• Structural Position: 69
• Q(SASA): 0.1716
• 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
N/S	None	None	0.999	N	0.611	0.333	0.218845423259	gnomAD-4.0.0	1.59283E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86094E-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
N/A	0.8544	likely_pathogenic	0.868	pathogenic	-1.113	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
N/C	0.6267	likely_pathogenic	0.6289	pathogenic	-0.261	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
N/D	0.8421	likely_pathogenic	0.8524	pathogenic	-0.944	Destabilizing	0.999	D	0.646	neutral	N	0.468116782	None	None	N
N/E	0.9672	likely_pathogenic	0.9639	pathogenic	-0.73	Destabilizing	0.999	D	0.724	prob.delet.	None	None	None	None	N
N/F	0.9788	likely_pathogenic	0.978	pathogenic	-0.611	Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	N
N/G	0.7952	likely_pathogenic	0.8008	pathogenic	-1.529	Destabilizing	0.999	D	0.599	neutral	None	None	None	None	N
N/H	0.6519	likely_pathogenic	0.653	pathogenic	-0.916	Destabilizing	1.0	D	0.773	deleterious	N	0.502552131	None	None	N
N/I	0.8784	likely_pathogenic	0.8806	pathogenic	-0.005	Destabilizing	1.0	D	0.804	deleterious	N	0.478080735	None	None	N
N/K	0.981	likely_pathogenic	0.9817	pathogenic	-0.076	Destabilizing	1.0	D	0.75	deleterious	N	0.51821223	None	None	N
N/L	0.8311	likely_pathogenic	0.8267	pathogenic	-0.005	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	N
N/M	0.9072	likely_pathogenic	0.9114	pathogenic	0.211	Stabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
N/P	0.9139	likely_pathogenic	0.9262	pathogenic	-0.346	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
N/Q	0.9238	likely_pathogenic	0.9236	pathogenic	-0.665	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
N/R	0.957	likely_pathogenic	0.9611	pathogenic	-0.234	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
N/S	0.2063	likely_benign	0.23	benign	-1.075	Destabilizing	0.999	D	0.611	neutral	N	0.50129855	None	None	N
N/T	0.4631	ambiguous	0.4978	ambiguous	-0.644	Destabilizing	0.999	D	0.707	prob.neutral	N	0.477074896	None	None	N
N/V	0.8433	likely_pathogenic	0.8458	pathogenic	-0.346	Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	N
N/W	0.9854	likely_pathogenic	0.9855	pathogenic	-0.337	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
N/Y	0.8658	likely_pathogenic	0.8629	pathogenic	-0.058	Destabilizing	1.0	D	0.8	deleterious	D	0.52327412	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.