TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16454	49585;49586;49587	chr2:178613923;178613922;178613921	chr2:179478650;179478649;179478648
N2AB	14813	44662;44663;44664	chr2:178613923;178613922;178613921	chr2:179478650;179478649;179478648
N2A	13886	41881;41882;41883	chr2:178613923;178613922;178613921	chr2:179478650;179478649;179478648
N2B	7389	22390;22391;22392	chr2:178613923;178613922;178613921	chr2:179478650;179478649;179478648
Novex-1	7514	22765;22766;22767	chr2:178613923;178613922;178613921	chr2:179478650;179478649;179478648
Novex-2	7581	22966;22967;22968	chr2:178613923;178613922;178613921	chr2:179478650;179478649;179478648
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: Fn3-7
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.1187
• 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/Q	None	None	1.0	D	0.869	0.601	0.647047692233	gnomAD-4.0.0	1.60554E-06	None	None	None	None	N	None	0	0	None	0	2.78365E-05	None	0	0	0	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	0.8585	likely_pathogenic	0.8755	pathogenic	-2.3	Highly Destabilizing	1.0	D	0.799	deleterious	D	0.68340191	None	None	N
P/C	0.9767	likely_pathogenic	0.9768	pathogenic	-2.258	Highly Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
P/D	0.9996	likely_pathogenic	0.9996	pathogenic	-3.405	Highly Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
P/E	0.9989	likely_pathogenic	0.999	pathogenic	-3.178	Highly Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
P/F	0.9996	likely_pathogenic	0.9997	pathogenic	-1.21	Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
P/G	0.9952	likely_pathogenic	0.9952	pathogenic	-2.809	Highly Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
P/H	0.9988	likely_pathogenic	0.999	pathogenic	-2.471	Highly Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
P/I	0.9804	likely_pathogenic	0.9777	pathogenic	-0.859	Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
P/K	0.9992	likely_pathogenic	0.9993	pathogenic	-1.883	Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
P/L	0.9676	likely_pathogenic	0.9695	pathogenic	-0.859	Destabilizing	1.0	D	0.895	deleterious	D	0.814831678	None	None	N
P/M	0.9948	likely_pathogenic	0.995	pathogenic	-1.291	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
P/N	0.9994	likely_pathogenic	0.9994	pathogenic	-2.349	Highly Destabilizing	1.0	D	0.909	deleterious	None	None	None	None	N
P/Q	0.9978	likely_pathogenic	0.9982	pathogenic	-2.172	Highly Destabilizing	1.0	D	0.869	deleterious	D	0.817882912	None	None	N
P/R	0.9972	likely_pathogenic	0.9975	pathogenic	-1.729	Destabilizing	1.0	D	0.911	deleterious	D	0.817243049	None	None	N
P/S	0.9914	likely_pathogenic	0.9928	pathogenic	-2.865	Highly Destabilizing	1.0	D	0.855	deleterious	D	0.784222619	None	None	N
P/T	0.982	likely_pathogenic	0.9817	pathogenic	-2.506	Highly Destabilizing	1.0	D	0.843	deleterious	D	0.783106606	None	None	N
P/V	0.9169	likely_pathogenic	0.9023	pathogenic	-1.317	Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
P/W	0.9999	likely_pathogenic	0.9999	pathogenic	-1.737	Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
P/Y	0.9998	likely_pathogenic	0.9998	pathogenic	-1.448	Destabilizing	1.0	D	0.901	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.