TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6349	19270;19271;19272	chr2:178728993;178728992;178728991	chr2:179593720;179593719;179593718
N2AB	6032	18319;18320;18321	chr2:178728993;178728992;178728991	chr2:179593720;179593719;179593718
N2A	5105	15538;15539;15540	chr2:178728993;178728992;178728991	chr2:179593720;179593719;179593718
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-47
• Domain position: 58
• Structural Position: 138
• Q(SASA): 0.0681
• 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
L/I	rs2079884280	None	0.688	D	0.706	0.398	0.591171394266	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
L/I	rs2079884280	None	0.688	D	0.706	0.398	0.591171394266	gnomAD-4.0.0	6.57428E-06	None	None	None	None	N	None	2.41383E-05	0	None	0	0	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
L/A	0.9149	likely_pathogenic	0.9258	pathogenic	-2.298	Highly Destabilizing	0.895	D	0.783	deleterious	None	None	None	None	N
L/C	0.8862	likely_pathogenic	0.8923	pathogenic	-1.56	Destabilizing	0.998	D	0.835	deleterious	None	None	None	None	N
L/D	0.9997	likely_pathogenic	0.9997	pathogenic	-3.092	Highly Destabilizing	0.997	D	0.911	deleterious	None	None	None	None	N
L/E	0.9971	likely_pathogenic	0.9976	pathogenic	-2.764	Highly Destabilizing	0.992	D	0.883	deleterious	None	None	None	None	N
L/F	0.4792	ambiguous	0.4995	ambiguous	-1.416	Destabilizing	0.978	D	0.785	deleterious	D	0.552969513	None	None	N
L/G	0.984	likely_pathogenic	0.9867	pathogenic	-2.897	Highly Destabilizing	0.992	D	0.885	deleterious	None	None	None	None	N
L/H	0.9864	likely_pathogenic	0.9889	pathogenic	-2.835	Highly Destabilizing	0.999	D	0.904	deleterious	D	0.57573503	None	None	N
L/I	0.2847	likely_benign	0.255	benign	-0.492	Destabilizing	0.688	D	0.706	prob.neutral	D	0.544549268	None	None	N
L/K	0.9932	likely_pathogenic	0.9946	pathogenic	-1.716	Destabilizing	0.992	D	0.885	deleterious	None	None	None	None	N
L/M	0.2935	likely_benign	0.324	benign	-0.756	Destabilizing	0.983	D	0.779	deleterious	None	None	None	None	N
L/N	0.9972	likely_pathogenic	0.9975	pathogenic	-2.482	Highly Destabilizing	0.997	D	0.911	deleterious	None	None	None	None	N
L/P	0.9974	likely_pathogenic	0.9976	pathogenic	-1.086	Destabilizing	0.996	D	0.905	deleterious	D	0.587091335	None	None	N
L/Q	0.978	likely_pathogenic	0.9837	pathogenic	-2.058	Highly Destabilizing	0.997	D	0.909	deleterious	None	None	None	None	N
L/R	0.9814	likely_pathogenic	0.984	pathogenic	-2.021	Highly Destabilizing	0.989	D	0.903	deleterious	D	0.587091335	None	None	N
L/S	0.9881	likely_pathogenic	0.9905	pathogenic	-2.958	Highly Destabilizing	0.983	D	0.879	deleterious	None	None	None	None	N
L/T	0.9734	likely_pathogenic	0.9769	pathogenic	-2.457	Highly Destabilizing	0.983	D	0.818	deleterious	None	None	None	None	N
L/V	0.2995	likely_benign	0.2973	benign	-1.086	Destabilizing	0.039	N	0.425	neutral	D	0.545816716	None	None	N
L/W	0.9576	likely_pathogenic	0.9608	pathogenic	-1.809	Destabilizing	0.999	D	0.879	deleterious	None	None	None	None	N
L/Y	0.957	likely_pathogenic	0.9585	pathogenic	-1.573	Destabilizing	0.992	D	0.839	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.