TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23894	71905;71906;71907	chr2:178574452;178574451;178574450	chr2:179439179;179439178;179439177
N2AB	22253	66982;66983;66984	chr2:178574452;178574451;178574450	chr2:179439179;179439178;179439177
N2A	21326	64201;64202;64203	chr2:178574452;178574451;178574450	chr2:179439179;179439178;179439177
N2B	14829	44710;44711;44712	chr2:178574452;178574451;178574450	chr2:179439179;179439178;179439177
Novex-1	14954	45085;45086;45087	chr2:178574452;178574451;178574450	chr2:179439179;179439178;179439177
Novex-2	15021	45286;45287;45288	chr2:178574452;178574451;178574450	chr2:179439179;179439178;179439177
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGT
• RefSeq wild type template codon: CCA
• Domain: Fn3-61
• Domain position: 69
• Structural Position: 100
• Q(SASA): 0.3854
• 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
G/C	None	None	1.0	D	0.823	0.711	0.878826326238	gnomAD-4.0.0	6.84289E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.09607E-06	0	1.65673E-05

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
G/A	0.5876	likely_pathogenic	0.5602	ambiguous	-0.471	Destabilizing	1.0	D	0.709	prob.delet.	N	0.494648643	None	None	N
G/C	0.6811	likely_pathogenic	0.6524	pathogenic	-0.826	Destabilizing	1.0	D	0.823	deleterious	D	0.557737274	None	None	N
G/D	0.812	likely_pathogenic	0.7753	pathogenic	-0.665	Destabilizing	1.0	D	0.808	deleterious	N	0.493305517	None	None	N
G/E	0.8577	likely_pathogenic	0.8191	pathogenic	-0.793	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
G/F	0.9573	likely_pathogenic	0.9489	pathogenic	-0.999	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
G/H	0.8442	likely_pathogenic	0.8379	pathogenic	-0.814	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
G/I	0.9572	likely_pathogenic	0.9435	pathogenic	-0.403	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
G/K	0.8951	likely_pathogenic	0.878	pathogenic	-1.042	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
G/L	0.9326	likely_pathogenic	0.9223	pathogenic	-0.403	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
G/M	0.9231	likely_pathogenic	0.9162	pathogenic	-0.391	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
G/N	0.6299	likely_pathogenic	0.6294	pathogenic	-0.666	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
G/P	0.9968	likely_pathogenic	0.9962	pathogenic	-0.388	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
G/Q	0.8088	likely_pathogenic	0.7973	pathogenic	-0.916	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
G/R	0.7798	likely_pathogenic	0.75	pathogenic	-0.602	Destabilizing	1.0	D	0.861	deleterious	D	0.52997178	None	None	N
G/S	0.2976	likely_benign	0.3031	benign	-0.865	Destabilizing	1.0	D	0.801	deleterious	N	0.502522228	None	None	N
G/T	0.7435	likely_pathogenic	0.7276	pathogenic	-0.918	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
G/V	0.9161	likely_pathogenic	0.8906	pathogenic	-0.388	Destabilizing	1.0	D	0.853	deleterious	D	0.545873989	None	None	N
G/W	0.9169	likely_pathogenic	0.8966	pathogenic	-1.227	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
G/Y	0.8983	likely_pathogenic	0.8867	pathogenic	-0.858	Destabilizing	1.0	D	0.822	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.