TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5828	17707;17708;17709	chr2:178731183;178731182;178731181	chr2:179595910;179595909;179595908
N2AB	5511	16756;16757;16758	chr2:178731183;178731182;178731181	chr2:179595910;179595909;179595908
N2A	4584	13975;13976;13977	chr2:178731183;178731182;178731181	chr2:179595910;179595909;179595908
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: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-42
• Domain position: 6
• Structural Position: 7
• Q(SASA): 0.7519
• 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
E/K	rs2080414407	None	0.011	N	0.145	0.162	0.322786055943	gnomAD-4.0.0	1.59254E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86087E-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
E/A	0.1035	likely_benign	0.1096	benign	-0.472	Destabilizing	0.896	D	0.501	neutral	N	0.49378908	None	None	N
E/C	0.8137	likely_pathogenic	0.8472	pathogenic	-0.131	Destabilizing	0.999	D	0.683	prob.neutral	None	None	None	None	N
E/D	0.1539	likely_benign	0.1605	benign	-0.506	Destabilizing	0.896	D	0.476	neutral	N	0.486795647	None	None	N
E/F	0.7534	likely_pathogenic	0.7788	pathogenic	-0.242	Destabilizing	0.996	D	0.633	neutral	None	None	None	None	N
E/G	0.1213	likely_benign	0.1448	benign	-0.717	Destabilizing	0.896	D	0.563	neutral	N	0.487287182	None	None	N
E/H	0.4547	ambiguous	0.4793	ambiguous	-0.195	Destabilizing	0.988	D	0.557	neutral	None	None	None	None	N
E/I	0.3694	ambiguous	0.3826	ambiguous	0.154	Stabilizing	0.988	D	0.636	neutral	None	None	None	None	N
E/K	0.0789	likely_benign	0.0862	benign	0.102	Stabilizing	0.011	N	0.145	neutral	N	0.418597888	None	None	N
E/L	0.3465	ambiguous	0.3704	ambiguous	0.154	Stabilizing	0.919	D	0.542	neutral	None	None	None	None	N
E/M	0.3716	ambiguous	0.387	ambiguous	0.281	Stabilizing	0.999	D	0.624	neutral	None	None	None	None	N
E/N	0.2311	likely_benign	0.2564	benign	-0.241	Destabilizing	0.919	D	0.519	neutral	None	None	None	None	N
E/P	0.3011	likely_benign	0.331	benign	-0.034	Destabilizing	0.988	D	0.556	neutral	None	None	None	None	N
E/Q	0.123	likely_benign	0.1212	benign	-0.182	Destabilizing	0.251	N	0.214	neutral	N	0.454462688	None	None	N
E/R	0.1755	likely_benign	0.1907	benign	0.317	Stabilizing	0.851	D	0.493	neutral	None	None	None	None	N
E/S	0.1878	likely_benign	0.2058	benign	-0.42	Destabilizing	0.919	D	0.487	neutral	None	None	None	None	N
E/T	0.174	likely_benign	0.1834	benign	-0.224	Destabilizing	0.919	D	0.542	neutral	None	None	None	None	N
E/V	0.1973	likely_benign	0.2049	benign	-0.034	Destabilizing	0.984	D	0.544	neutral	D	0.523591912	None	None	N
E/W	0.8845	likely_pathogenic	0.9012	pathogenic	-0.064	Destabilizing	0.999	D	0.699	prob.neutral	None	None	None	None	N
E/Y	0.579	likely_pathogenic	0.6144	pathogenic	0.002	Stabilizing	0.996	D	0.63	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.