TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22879	68860;68861;68862	chr2:178577791;178577790;178577789	chr2:179442518;179442517;179442516
N2AB	21238	63937;63938;63939	chr2:178577791;178577790;178577789	chr2:179442518;179442517;179442516
N2A	20311	61156;61157;61158	chr2:178577791;178577790;178577789	chr2:179442518;179442517;179442516
N2B	13814	41665;41666;41667	chr2:178577791;178577790;178577789	chr2:179442518;179442517;179442516
Novex-1	13939	42040;42041;42042	chr2:178577791;178577790;178577789	chr2:179442518;179442517;179442516
Novex-2	14006	42241;42242;42243	chr2:178577791;178577790;178577789	chr2:179442518;179442517;179442516
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-54
• Domain position: 39
• Structural Position: 41
• Q(SASA): 0.0959
• 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
E/K	rs373765319	-2.378	0.999	D	0.673	0.481	None	gnomAD-2.1.1	8.08E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.79E-05	0
E/K	rs373765319	-2.378	0.999	D	0.673	0.481	None	gnomAD-4.0.0	6.37042E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.14405E-05	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
E/A	0.9717	likely_pathogenic	0.9769	pathogenic	-2.147	Highly Destabilizing	0.999	D	0.743	deleterious	D	0.542433133	None	None	N
E/C	0.994	likely_pathogenic	0.9947	pathogenic	-1.234	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
E/D	0.9264	likely_pathogenic	0.9481	pathogenic	-2.02	Highly Destabilizing	0.999	D	0.674	neutral	N	0.501376004	None	None	N
E/F	0.9962	likely_pathogenic	0.997	pathogenic	-1.846	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
E/G	0.9733	likely_pathogenic	0.9746	pathogenic	-2.497	Highly Destabilizing	1.0	D	0.801	deleterious	D	0.544207559	None	None	N
E/H	0.9909	likely_pathogenic	0.9929	pathogenic	-1.642	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
E/I	0.9889	likely_pathogenic	0.9915	pathogenic	-1.123	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
E/K	0.9752	likely_pathogenic	0.9781	pathogenic	-2.151	Highly Destabilizing	0.999	D	0.673	neutral	D	0.536392745	None	None	N
E/L	0.9867	likely_pathogenic	0.989	pathogenic	-1.123	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
E/M	0.9862	likely_pathogenic	0.9888	pathogenic	-0.33	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
E/N	0.994	likely_pathogenic	0.9955	pathogenic	-2.271	Highly Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
E/P	0.9998	likely_pathogenic	0.9998	pathogenic	-1.455	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
E/Q	0.8396	likely_pathogenic	0.8649	pathogenic	-1.996	Destabilizing	1.0	D	0.764	deleterious	N	0.484864684	None	None	N
E/R	0.9785	likely_pathogenic	0.9813	pathogenic	-1.872	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
E/S	0.9742	likely_pathogenic	0.9798	pathogenic	-2.912	Highly Destabilizing	0.999	D	0.737	prob.delet.	None	None	None	None	N
E/T	0.9873	likely_pathogenic	0.9898	pathogenic	-2.575	Highly Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
E/V	0.9754	likely_pathogenic	0.9812	pathogenic	-1.455	Destabilizing	1.0	D	0.805	deleterious	D	0.53479981	None	None	N
E/W	0.9969	likely_pathogenic	0.9974	pathogenic	-1.913	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
E/Y	0.9927	likely_pathogenic	0.994	pathogenic	-1.709	Destabilizing	1.0	D	0.834	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.