TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19980	60163;60164;60165	chr2:178591881;178591880;178591879	chr2:179456608;179456607;179456606
N2AB	18339	55240;55241;55242	chr2:178591881;178591880;178591879	chr2:179456608;179456607;179456606
N2A	17412	52459;52460;52461	chr2:178591881;178591880;178591879	chr2:179456608;179456607;179456606
N2B	10915	32968;32969;32970	chr2:178591881;178591880;178591879	chr2:179456608;179456607;179456606
Novex-1	11040	33343;33344;33345	chr2:178591881;178591880;178591879	chr2:179456608;179456607;179456606
Novex-2	11107	33544;33545;33546	chr2:178591881;178591880;178591879	chr2:179456608;179456607;179456606
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-33
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.2872
• 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
P/A	None	None	1.0	N	0.839	0.345	0.301122078929	gnomAD-4.0.0	1.60523E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86959E-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
P/A	0.1719	likely_benign	0.1753	benign	-1.743	Destabilizing	1.0	D	0.839	deleterious	N	0.471511574	None	None	N
P/C	0.7521	likely_pathogenic	0.778	pathogenic	-1.14	Destabilizing	1.0	D	0.868	deleterious	None	None	None	None	N
P/D	0.9226	likely_pathogenic	0.931	pathogenic	-2.268	Highly Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
P/E	0.7518	likely_pathogenic	0.7803	pathogenic	-2.262	Highly Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
P/F	0.7889	likely_pathogenic	0.8077	pathogenic	-1.358	Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
P/G	0.7572	likely_pathogenic	0.7565	pathogenic	-2.067	Highly Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
P/H	0.5273	ambiguous	0.5487	ambiguous	-1.687	Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	N
P/I	0.5822	likely_pathogenic	0.6069	pathogenic	-0.926	Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
P/K	0.5948	likely_pathogenic	0.6174	pathogenic	-1.479	Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
P/L	0.3646	ambiguous	0.3668	ambiguous	-0.926	Destabilizing	1.0	D	0.89	deleterious	N	0.515089394	None	None	N
P/M	0.6039	likely_pathogenic	0.6241	pathogenic	-0.666	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
P/N	0.7882	likely_pathogenic	0.8091	pathogenic	-1.304	Destabilizing	1.0	D	0.896	deleterious	None	None	None	None	N
P/Q	0.4455	ambiguous	0.4617	ambiguous	-1.506	Destabilizing	1.0	D	0.847	deleterious	N	0.501794078	None	None	N
P/R	0.448	ambiguous	0.4427	ambiguous	-0.933	Destabilizing	1.0	D	0.897	deleterious	N	0.499832295	None	None	N
P/S	0.3927	ambiguous	0.4088	ambiguous	-1.72	Destabilizing	1.0	D	0.84	deleterious	N	0.476852968	None	None	N
P/T	0.3754	ambiguous	0.4055	ambiguous	-1.621	Destabilizing	1.0	D	0.83	deleterious	N	0.514582415	None	None	N
P/V	0.4527	ambiguous	0.4795	ambiguous	-1.168	Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	N
P/W	0.9302	likely_pathogenic	0.9336	pathogenic	-1.616	Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	N
P/Y	0.797	likely_pathogenic	0.8199	pathogenic	-1.356	Destabilizing	1.0	D	0.904	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.