TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24057	72394;72395;72396	chr2:178573963;178573962;178573961	chr2:179438690;179438689;179438688
N2AB	22416	67471;67472;67473	chr2:178573963;178573962;178573961	chr2:179438690;179438689;179438688
N2A	21489	64690;64691;64692	chr2:178573963;178573962;178573961	chr2:179438690;179438689;179438688
N2B	14992	45199;45200;45201	chr2:178573963;178573962;178573961	chr2:179438690;179438689;179438688
Novex-1	15117	45574;45575;45576	chr2:178573963;178573962;178573961	chr2:179438690;179438689;179438688
Novex-2	15184	45775;45776;45777	chr2:178573963;178573962;178573961	chr2:179438690;179438689;179438688
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: Ig-131
• Domain position: 29
• Structural Position: 42
• Q(SASA): 0.271
• 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/L	rs781601295	-0.49	1.0	D	0.779	0.688	0.898687159605	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
P/Q	None	None	1.0	D	0.8	0.694	0.813645464229	gnomAD-4.0.0	6.84388E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99594E-07	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	0.9141	likely_pathogenic	0.8898	pathogenic	-0.61	Destabilizing	1.0	D	0.741	deleterious	D	0.560468385	None	None	I
P/C	0.9906	likely_pathogenic	0.9867	pathogenic	-0.532	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	I
P/D	0.9849	likely_pathogenic	0.9775	pathogenic	-0.612	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	I
P/E	0.9799	likely_pathogenic	0.9738	pathogenic	-0.716	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	I
P/F	0.9875	likely_pathogenic	0.983	pathogenic	-0.791	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	I
P/G	0.9801	likely_pathogenic	0.9738	pathogenic	-0.764	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	I
P/H	0.9586	likely_pathogenic	0.945	pathogenic	-0.375	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	I
P/I	0.918	likely_pathogenic	0.9138	pathogenic	-0.343	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	I
P/K	0.9766	likely_pathogenic	0.9704	pathogenic	-0.627	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	I
P/L	0.8513	likely_pathogenic	0.8188	pathogenic	-0.343	Destabilizing	1.0	D	0.779	deleterious	D	0.624547487	None	None	I
P/M	0.9592	likely_pathogenic	0.9498	pathogenic	-0.367	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	I
P/N	0.9781	likely_pathogenic	0.9686	pathogenic	-0.291	Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	I
P/Q	0.9606	likely_pathogenic	0.9508	pathogenic	-0.541	Destabilizing	1.0	D	0.8	deleterious	D	0.575445542	None	None	I
P/R	0.9559	likely_pathogenic	0.9448	pathogenic	-0.079	Destabilizing	1.0	D	0.799	deleterious	D	0.656182601	None	None	I
P/S	0.965	likely_pathogenic	0.9495	pathogenic	-0.606	Destabilizing	1.0	D	0.775	deleterious	D	0.586294868	None	None	I
P/T	0.9203	likely_pathogenic	0.8955	pathogenic	-0.614	Destabilizing	1.0	D	0.769	deleterious	D	0.624143879	None	None	I
P/V	0.9045	likely_pathogenic	0.8923	pathogenic	-0.398	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	I
P/W	0.9954	likely_pathogenic	0.9947	pathogenic	-0.897	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	I
P/Y	0.9856	likely_pathogenic	0.98	pathogenic	-0.608	Destabilizing	1.0	D	0.828	deleterious	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.