TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19981	60166;60167;60168	chr2:178591878;178591877;178591876	chr2:179456605;179456604;179456603
N2AB	18340	55243;55244;55245	chr2:178591878;178591877;178591876	chr2:179456605;179456604;179456603
N2A	17413	52462;52463;52464	chr2:178591878;178591877;178591876	chr2:179456605;179456604;179456603
N2B	10916	32971;32972;32973	chr2:178591878;178591877;178591876	chr2:179456605;179456604;179456603
Novex-1	11041	33346;33347;33348	chr2:178591878;178591877;178591876	chr2:179456605;179456604;179456603
Novex-2	11108	33547;33548;33549	chr2:178591878;178591877;178591876	chr2:179456605;179456604;179456603
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Fn3-33
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.1115
• 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/L	None	None	1.0	D	0.927	0.565	0.82662405614	gnomAD-4.0.0	1.59822E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	2.42483E-04	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	0.7662	likely_pathogenic	0.8404	pathogenic	-2.392	Highly Destabilizing	1.0	D	0.855	deleterious	N	0.521431811	None	None	N
P/C	0.9483	likely_pathogenic	0.9715	pathogenic	-2.088	Highly Destabilizing	1.0	D	0.913	deleterious	None	None	None	None	N
P/D	0.9995	likely_pathogenic	0.9997	pathogenic	-3.372	Highly Destabilizing	1.0	D	0.892	deleterious	None	None	None	None	N
P/E	0.9975	likely_pathogenic	0.9984	pathogenic	-3.108	Highly Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
P/F	0.9981	likely_pathogenic	0.9991	pathogenic	-1.129	Destabilizing	1.0	D	0.934	deleterious	None	None	None	None	N
P/G	0.9929	likely_pathogenic	0.9951	pathogenic	-2.924	Highly Destabilizing	1.0	D	0.918	deleterious	None	None	None	None	N
P/H	0.9966	likely_pathogenic	0.9982	pathogenic	-2.654	Highly Destabilizing	1.0	D	0.897	deleterious	D	0.570010584	None	None	N
P/I	0.7705	likely_pathogenic	0.8684	pathogenic	-0.858	Destabilizing	1.0	D	0.943	deleterious	None	None	None	None	N
P/K	0.9974	likely_pathogenic	0.9985	pathogenic	-1.911	Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
P/L	0.8392	likely_pathogenic	0.9053	pathogenic	-0.858	Destabilizing	1.0	D	0.927	deleterious	D	0.568236157	None	None	N
P/M	0.9709	likely_pathogenic	0.9844	pathogenic	-1.255	Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
P/N	0.9984	likely_pathogenic	0.9992	pathogenic	-2.433	Highly Destabilizing	1.0	D	0.943	deleterious	None	None	None	None	N
P/Q	0.993	likely_pathogenic	0.996	pathogenic	-2.161	Highly Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	N
P/R	0.9915	likely_pathogenic	0.9952	pathogenic	-1.849	Destabilizing	1.0	D	0.945	deleterious	D	0.569503605	None	None	N
P/S	0.9783	likely_pathogenic	0.9876	pathogenic	-2.934	Highly Destabilizing	1.0	D	0.896	deleterious	D	0.55165284	None	None	N
P/T	0.9117	likely_pathogenic	0.9484	pathogenic	-2.54	Highly Destabilizing	1.0	D	0.889	deleterious	D	0.557640321	None	None	N
P/V	0.522	ambiguous	0.6597	pathogenic	-1.351	Destabilizing	1.0	D	0.923	deleterious	None	None	None	None	N
P/W	0.9996	likely_pathogenic	0.9998	pathogenic	-1.719	Destabilizing	1.0	D	0.913	deleterious	None	None	None	None	N
P/Y	0.9991	likely_pathogenic	0.9996	pathogenic	-1.468	Destabilizing	1.0	D	0.941	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.