TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29667	89224;89225;89226	chr2:178554112;178554111;178554110	chr2:179418839;179418838;179418837
N2AB	28026	84301;84302;84303	chr2:178554112;178554111;178554110	chr2:179418839;179418838;179418837
N2A	27099	81520;81521;81522	chr2:178554112;178554111;178554110	chr2:179418839;179418838;179418837
N2B	20602	62029;62030;62031	chr2:178554112;178554111;178554110	chr2:179418839;179418838;179418837
Novex-1	20727	62404;62405;62406	chr2:178554112;178554111;178554110	chr2:179418839;179418838;179418837
Novex-2	20794	62605;62606;62607	chr2:178554112;178554111;178554110	chr2:179418839;179418838;179418837
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Fn3-104
• Domain position: 35
• Structural Position: 37
• Q(SASA): 0.1471
• 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
G/R	None	None	1.0	N	0.917	0.526	0.702643714836	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
G/A	0.3809	ambiguous	0.4467	ambiguous	-0.189	Destabilizing	1.0	D	0.593	neutral	N	0.500912386	None	None	N
G/C	0.5135	ambiguous	0.6043	pathogenic	-0.436	Destabilizing	1.0	D	0.827	deleterious	D	0.527045265	None	None	N
G/D	0.8585	likely_pathogenic	0.8896	pathogenic	-0.523	Destabilizing	1.0	D	0.863	deleterious	N	0.505445063	None	None	N
G/E	0.8862	likely_pathogenic	0.9204	pathogenic	-0.426	Destabilizing	1.0	D	0.924	deleterious	None	None	None	None	N
G/F	0.93	likely_pathogenic	0.957	pathogenic	-0.278	Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	N
G/H	0.8527	likely_pathogenic	0.8943	pathogenic	-1.166	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
G/I	0.9274	likely_pathogenic	0.9594	pathogenic	0.653	Stabilizing	1.0	D	0.892	deleterious	None	None	None	None	N
G/K	0.9518	likely_pathogenic	0.9675	pathogenic	-0.337	Destabilizing	1.0	D	0.925	deleterious	None	None	None	None	N
G/L	0.9121	likely_pathogenic	0.949	pathogenic	0.653	Stabilizing	1.0	D	0.921	deleterious	None	None	None	None	N
G/M	0.9212	likely_pathogenic	0.9509	pathogenic	0.293	Stabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
G/N	0.6662	likely_pathogenic	0.7177	pathogenic	-0.335	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
G/P	0.998	likely_pathogenic	0.9991	pathogenic	0.417	Stabilizing	1.0	D	0.915	deleterious	None	None	None	None	N
G/Q	0.8468	likely_pathogenic	0.894	pathogenic	-0.223	Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
G/R	0.8679	likely_pathogenic	0.9093	pathogenic	-0.584	Destabilizing	1.0	D	0.917	deleterious	N	0.499240091	None	None	N
G/S	0.2266	likely_benign	0.278	benign	-0.753	Destabilizing	1.0	D	0.677	prob.neutral	N	0.485971228	None	None	N
G/T	0.6394	likely_pathogenic	0.7351	pathogenic	-0.535	Destabilizing	1.0	D	0.924	deleterious	None	None	None	None	N
G/V	0.8544	likely_pathogenic	0.9142	pathogenic	0.417	Stabilizing	1.0	D	0.924	deleterious	D	0.552275863	None	None	N
G/W	0.9046	likely_pathogenic	0.943	pathogenic	-0.926	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
G/Y	0.86	likely_pathogenic	0.906	pathogenic	-0.286	Destabilizing	1.0	D	0.884	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.