TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7903	23932;23933;23934	chr2:178719785;178719784;178719783	chr2:179584512;179584511;179584510
N2AB	7586	22981;22982;22983	chr2:178719785;178719784;178719783	chr2:179584512;179584511;179584510
N2A	6659	20200;20201;20202	chr2:178719785;178719784;178719783	chr2:179584512;179584511;179584510
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-64
• Domain position: 15
• Structural Position: 24
• Q(SASA): 0.165
• 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/E	rs1362459833	-1.609	1.0	D	0.879	0.598	0.832462731495	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	6.47E-05	0	None	0	0	None	0	None	0	0	0
G/E	rs1362459833	-1.609	1.0	D	0.879	0.598	0.832462731495	gnomAD-4.0.0	6.84411E-07	None	None	None	None	N	None	2.98954E-05	0	None	0	0	None	0	0	0	0	0
G/V	None	None	1.0	D	0.884	0.622	0.941585166729	gnomAD-4.0.0	6.84411E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99713E-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
G/A	0.3883	ambiguous	0.3693	ambiguous	-0.391	Destabilizing	0.997	D	0.635	neutral	D	0.630326577	None	None	N
G/C	0.5852	likely_pathogenic	0.5592	ambiguous	-0.832	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
G/D	0.3801	ambiguous	0.355	ambiguous	-0.838	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
G/E	0.4008	ambiguous	0.3915	ambiguous	-1.012	Destabilizing	1.0	D	0.879	deleterious	D	0.612894586	None	None	N
G/F	0.8951	likely_pathogenic	0.8732	pathogenic	-1.187	Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
G/H	0.6357	likely_pathogenic	0.6087	pathogenic	-0.644	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
G/I	0.8747	likely_pathogenic	0.84	pathogenic	-0.541	Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	N
G/K	0.5287	ambiguous	0.5265	ambiguous	-0.858	Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
G/L	0.8081	likely_pathogenic	0.7867	pathogenic	-0.541	Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
G/M	0.8342	likely_pathogenic	0.8085	pathogenic	-0.387	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
G/N	0.42	ambiguous	0.4071	ambiguous	-0.492	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
G/P	0.986	likely_pathogenic	0.984	pathogenic	-0.458	Destabilizing	1.0	D	0.872	deleterious	None	None	None	None	N
G/Q	0.4539	ambiguous	0.4493	ambiguous	-0.84	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
G/R	0.3789	ambiguous	0.3684	ambiguous	-0.35	Destabilizing	1.0	D	0.875	deleterious	D	0.619616643	None	None	N
G/S	0.186	likely_benign	0.1802	benign	-0.608	Destabilizing	0.986	D	0.553	neutral	None	None	None	None	N
G/T	0.5122	ambiguous	0.4781	ambiguous	-0.723	Destabilizing	0.999	D	0.863	deleterious	None	None	None	None	N
G/V	0.7643	likely_pathogenic	0.7189	pathogenic	-0.458	Destabilizing	1.0	D	0.884	deleterious	D	0.668108695	None	None	N
G/W	0.7515	likely_pathogenic	0.7212	pathogenic	-1.319	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
G/Y	0.8026	likely_pathogenic	0.7753	pathogenic	-0.976	Destabilizing	1.0	D	0.893	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.