TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23125	69598;69599;69600	chr2:178576962;178576961;178576960	chr2:179441689;179441688;179441687
N2AB	21484	64675;64676;64677	chr2:178576962;178576961;178576960	chr2:179441689;179441688;179441687
N2A	20557	61894;61895;61896	chr2:178576962;178576961;178576960	chr2:179441689;179441688;179441687
N2B	14060	42403;42404;42405	chr2:178576962;178576961;178576960	chr2:179441689;179441688;179441687
Novex-1	14185	42778;42779;42780	chr2:178576962;178576961;178576960	chr2:179441689;179441688;179441687
Novex-2	14252	42979;42980;42981	chr2:178576962;178576961;178576960	chr2:179441689;179441688;179441687
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-55
• Domain position: 86
• Structural Position: 120
• Q(SASA): 0.3129
• Predicted PPI site: I

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/S	None	None	0.159	N	0.293	0.37	0.260735089382	gnomAD-4.0.0	1.59197E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43308E-05	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	0.0695	likely_benign	0.0663	benign	-1.561	Destabilizing	0.704	D	0.511	neutral	N	0.481671452	None	None	I
P/C	0.4854	ambiguous	0.4345	ambiguous	-0.952	Destabilizing	0.999	D	0.669	neutral	None	None	None	None	I
P/D	0.7726	likely_pathogenic	0.7472	pathogenic	-1.453	Destabilizing	0.939	D	0.521	neutral	None	None	None	None	I
P/E	0.628	likely_pathogenic	0.6001	pathogenic	-1.474	Destabilizing	0.939	D	0.523	neutral	None	None	None	None	I
P/F	0.516	ambiguous	0.4862	ambiguous	-1.217	Destabilizing	0.1	N	0.552	neutral	None	None	None	None	I
P/G	0.3928	ambiguous	0.3342	benign	-1.858	Destabilizing	0.939	D	0.527	neutral	None	None	None	None	I
P/H	0.3856	ambiguous	0.3682	ambiguous	-1.331	Destabilizing	0.999	D	0.634	neutral	D	0.53669546	None	None	I
P/I	0.4902	ambiguous	0.5119	ambiguous	-0.849	Destabilizing	0.884	D	0.592	neutral	None	None	None	None	I
P/K	0.7961	likely_pathogenic	0.7605	pathogenic	-1.294	Destabilizing	0.939	D	0.521	neutral	None	None	None	None	I
P/L	0.3049	likely_benign	0.3272	benign	-0.849	Destabilizing	0.704	D	0.533	neutral	D	0.522639675	None	None	I
P/M	0.4139	ambiguous	0.4159	ambiguous	-0.607	Destabilizing	0.991	D	0.641	neutral	None	None	None	None	I
P/N	0.5995	likely_pathogenic	0.5777	pathogenic	-1.008	Destabilizing	0.982	D	0.618	neutral	None	None	None	None	I
P/Q	0.4227	ambiguous	0.406	ambiguous	-1.235	Destabilizing	0.991	D	0.577	neutral	None	None	None	None	I
P/R	0.6595	likely_pathogenic	0.6438	pathogenic	-0.691	Destabilizing	0.988	D	0.621	neutral	N	0.520539761	None	None	I
P/S	0.1585	likely_benign	0.1523	benign	-1.497	Destabilizing	0.159	N	0.293	neutral	N	0.517070268	None	None	I
P/T	0.1753	likely_benign	0.18	benign	-1.42	Destabilizing	0.852	D	0.497	neutral	N	0.517830737	None	None	I
P/V	0.3167	likely_benign	0.3256	benign	-1.053	Destabilizing	0.17	N	0.521	neutral	None	None	None	None	I
P/W	0.7085	likely_pathogenic	0.6872	pathogenic	-1.357	Destabilizing	0.999	D	0.699	prob.neutral	None	None	None	None	I
P/Y	0.5185	ambiguous	0.4924	ambiguous	-1.114	Destabilizing	0.964	D	0.653	neutral	None	None	None	None	I

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.