TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24006	72241;72242;72243	chr2:178574116;178574115;178574114	chr2:179438843;179438842;179438841
N2AB	22365	67318;67319;67320	chr2:178574116;178574115;178574114	chr2:179438843;179438842;179438841
N2A	21438	64537;64538;64539	chr2:178574116;178574115;178574114	chr2:179438843;179438842;179438841
N2B	14941	45046;45047;45048	chr2:178574116;178574115;178574114	chr2:179438843;179438842;179438841
Novex-1	15066	45421;45422;45423	chr2:178574116;178574115;178574114	chr2:179438843;179438842;179438841
Novex-2	15133	45622;45623;45624	chr2:178574116;178574115;178574114	chr2:179438843;179438842;179438841
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: Fn3-62
• Domain position: 83
• Structural Position: 115
• Q(SASA): 0.292
• 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
G/A	None	None	1.0	D	0.741	0.722	0.482500522706	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05
G/D	rs779849818	-0.327	1.0	D	0.898	0.747	0.515317749148	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	5.58E-05	None	0	None	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
G/A	0.4646	ambiguous	0.5577	ambiguous	-0.348	Destabilizing	1.0	D	0.741	deleterious	D	0.538352345	None	None	I
G/C	0.629	likely_pathogenic	0.7029	pathogenic	-0.896	Destabilizing	1.0	D	0.853	deleterious	D	0.565864349	None	None	I
G/D	0.5728	likely_pathogenic	0.6654	pathogenic	-0.734	Destabilizing	1.0	D	0.898	deleterious	D	0.526235571	None	None	I
G/E	0.6614	likely_pathogenic	0.7591	pathogenic	-0.89	Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	I
G/F	0.9118	likely_pathogenic	0.9448	pathogenic	-1.02	Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	I
G/H	0.8171	likely_pathogenic	0.8644	pathogenic	-0.559	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	I
G/I	0.8941	likely_pathogenic	0.932	pathogenic	-0.45	Destabilizing	1.0	D	0.892	deleterious	None	None	None	None	I
G/K	0.8687	likely_pathogenic	0.9119	pathogenic	-0.957	Destabilizing	1.0	D	0.898	deleterious	None	None	None	None	I
G/L	0.8333	likely_pathogenic	0.8853	pathogenic	-0.45	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	I
G/M	0.8592	likely_pathogenic	0.9057	pathogenic	-0.505	Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	I
G/N	0.5183	ambiguous	0.5878	pathogenic	-0.6	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	I
G/P	0.994	likely_pathogenic	0.9966	pathogenic	-0.382	Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	I
G/Q	0.7176	likely_pathogenic	0.7743	pathogenic	-0.886	Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	I
G/R	0.7636	likely_pathogenic	0.8341	pathogenic	-0.46	Destabilizing	1.0	D	0.908	deleterious	D	0.541466217	None	None	I
G/S	0.254	likely_benign	0.3246	benign	-0.735	Destabilizing	1.0	D	0.841	deleterious	N	0.5208932	None	None	I
G/T	0.6524	likely_pathogenic	0.7354	pathogenic	-0.822	Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	I
G/V	0.7934	likely_pathogenic	0.8633	pathogenic	-0.382	Destabilizing	1.0	D	0.883	deleterious	D	0.536150299	None	None	I
G/W	0.8682	likely_pathogenic	0.916	pathogenic	-1.186	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	I
G/Y	0.8358	likely_pathogenic	0.8855	pathogenic	-0.843	Destabilizing	1.0	D	0.885	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.