TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30255	90988;90989;90990	chr2:178552137;178552136;178552135	chr2:179416864;179416863;179416862
N2AB	28614	86065;86066;86067	chr2:178552137;178552136;178552135	chr2:179416864;179416863;179416862
N2A	27687	83284;83285;83286	chr2:178552137;178552136;178552135	chr2:179416864;179416863;179416862
N2B	21190	63793;63794;63795	chr2:178552137;178552136;178552135	chr2:179416864;179416863;179416862
Novex-1	21315	64168;64169;64170	chr2:178552137;178552136;178552135	chr2:179416864;179416863;179416862
Novex-2	21382	64369;64370;64371	chr2:178552137;178552136;178552135	chr2:179416864;179416863;179416862
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Fn3-108
• Domain position: 32
• Structural Position: 33
• Q(SASA): 0.2316
• 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/R	rs775441664	-0.53	0.997	N	0.835	0.401	0.52437609879	gnomAD-2.1.1	8.05E-06	None	None	None	None	I	None	0	5.81E-05	None	0	0	None	0	None	0	0	0
G/R	rs775441664	-0.53	0.997	N	0.835	0.401	0.52437609879	gnomAD-4.0.0	4.78952E-06	None	None	None	None	I	None	0	4.47347E-05	None	0	0	None	0	0	4.49728E-06	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	0.2	likely_benign	0.1823	benign	-0.753	Destabilizing	0.117	N	0.565	neutral	N	0.388922768	None	None	I
G/C	0.3454	ambiguous	0.3156	benign	-0.916	Destabilizing	0.999	D	0.816	deleterious	None	None	None	None	I
G/D	0.8026	likely_pathogenic	0.7223	pathogenic	-0.994	Destabilizing	0.995	D	0.833	deleterious	None	None	None	None	I
G/E	0.7922	likely_pathogenic	0.7183	pathogenic	-1.077	Destabilizing	0.993	D	0.835	deleterious	N	0.4749256	None	None	I
G/F	0.9168	likely_pathogenic	0.8907	pathogenic	-1.191	Destabilizing	0.999	D	0.824	deleterious	None	None	None	None	I
G/H	0.8965	likely_pathogenic	0.8578	pathogenic	-1.274	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	I
G/I	0.7167	likely_pathogenic	0.6621	pathogenic	-0.465	Destabilizing	0.995	D	0.82	deleterious	None	None	None	None	I
G/K	0.9487	likely_pathogenic	0.9286	pathogenic	-1.123	Destabilizing	0.995	D	0.838	deleterious	None	None	None	None	I
G/L	0.8109	likely_pathogenic	0.7642	pathogenic	-0.465	Destabilizing	0.995	D	0.818	deleterious	None	None	None	None	I
G/M	0.7981	likely_pathogenic	0.7562	pathogenic	-0.349	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	I
G/N	0.7346	likely_pathogenic	0.6586	pathogenic	-0.755	Destabilizing	0.995	D	0.825	deleterious	None	None	None	None	I
G/P	0.9933	likely_pathogenic	0.9917	pathogenic	-0.521	Destabilizing	0.998	D	0.837	deleterious	None	None	None	None	I
G/Q	0.8416	likely_pathogenic	0.7867	pathogenic	-0.978	Destabilizing	0.998	D	0.831	deleterious	None	None	None	None	I
G/R	0.8824	likely_pathogenic	0.8468	pathogenic	-0.783	Destabilizing	0.997	D	0.835	deleterious	N	0.456801199	None	None	I
G/S	0.1395	likely_benign	0.1197	benign	-1.028	Destabilizing	0.835	D	0.564	neutral	None	None	None	None	I
G/T	0.3429	ambiguous	0.2922	benign	-1.03	Destabilizing	0.99	D	0.818	deleterious	None	None	None	None	I
G/V	0.5333	ambiguous	0.4749	ambiguous	-0.521	Destabilizing	0.987	D	0.818	deleterious	N	0.496090306	None	None	I
G/W	0.863	likely_pathogenic	0.844	pathogenic	-1.475	Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	I
G/Y	0.8932	likely_pathogenic	0.8635	pathogenic	-1.083	Destabilizing	1.0	D	0.826	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.