TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28056	84391;84392;84393	chr2:178561966;178561965;178561964	chr2:179426693;179426692;179426691
N2AB	26415	79468;79469;79470	chr2:178561966;178561965;178561964	chr2:179426693;179426692;179426691
N2A	25488	76687;76688;76689	chr2:178561966;178561965;178561964	chr2:179426693;179426692;179426691
N2B	18991	57196;57197;57198	chr2:178561966;178561965;178561964	chr2:179426693;179426692;179426691
Novex-1	19116	57571;57572;57573	chr2:178561966;178561965;178561964	chr2:179426693;179426692;179426691
Novex-2	19183	57772;57773;57774	chr2:178561966;178561965;178561964	chr2:179426693;179426692;179426691
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: Fn3-92
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.0991
• 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	0.999	D	0.843	0.593	0.782029222942	gnomAD-4.0.0	1.59315E-06	None	None	None	None	N	None	0	0	None	0	2.78272E-05	None	0	0	0	0	0
P/Q	None	None	1.0	D	0.859	0.581	0.835843738737	gnomAD-4.0.0	1.59324E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86236E-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	0.9243	likely_pathogenic	0.908	pathogenic	-1.996	Destabilizing	0.999	D	0.843	deleterious	D	0.639557777	None	None	N
P/C	0.9937	likely_pathogenic	0.9916	pathogenic	-2.255	Highly Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
P/D	0.9986	likely_pathogenic	0.9981	pathogenic	-3.433	Highly Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
P/E	0.9965	likely_pathogenic	0.9958	pathogenic	-3.307	Highly Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
P/F	0.9995	likely_pathogenic	0.9994	pathogenic	-1.172	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
P/G	0.994	likely_pathogenic	0.9924	pathogenic	-2.355	Highly Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
P/H	0.9968	likely_pathogenic	0.9963	pathogenic	-1.739	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	N
P/I	0.9914	likely_pathogenic	0.9892	pathogenic	-1.025	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
P/K	0.9971	likely_pathogenic	0.9965	pathogenic	-1.739	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
P/L	0.9675	likely_pathogenic	0.9766	pathogenic	-1.025	Destabilizing	1.0	D	0.825	deleterious	D	0.651801782	None	None	N
P/M	0.9964	likely_pathogenic	0.9954	pathogenic	-1.411	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
P/N	0.9987	likely_pathogenic	0.9983	pathogenic	-2.113	Highly Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
P/Q	0.9955	likely_pathogenic	0.9946	pathogenic	-2.147	Highly Destabilizing	1.0	D	0.859	deleterious	D	0.677541698	None	None	N
P/R	0.9914	likely_pathogenic	0.9897	pathogenic	-1.367	Destabilizing	1.0	D	0.837	deleterious	D	0.661320533	None	None	N
P/S	0.9916	likely_pathogenic	0.9937	pathogenic	-2.491	Highly Destabilizing	1.0	D	0.819	deleterious	D	0.661118729	None	None	N
P/T	0.9847	likely_pathogenic	0.9814	pathogenic	-2.261	Highly Destabilizing	1.0	D	0.833	deleterious	D	0.677339894	None	None	N
P/V	0.9795	likely_pathogenic	0.9741	pathogenic	-1.326	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
P/W	0.9997	likely_pathogenic	0.9996	pathogenic	-1.527	Destabilizing	1.0	D	0.736	deleterious	None	None	None	None	N
P/Y	0.9993	likely_pathogenic	0.9992	pathogenic	-1.271	Destabilizing	1.0	D	0.819	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.