TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6944	21055;21056;21057	chr2:178725374;178725373;178725372	chr2:179590101;179590100;179590099
N2AB	6627	20104;20105;20106	chr2:178725374;178725373;178725372	chr2:179590101;179590100;179590099
N2A	5700	17323;17324;17325	chr2:178725374;178725373;178725372	chr2:179590101;179590100;179590099
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: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-53
• Domain position: 91
• Structural Position: 178
• Q(SASA): 0.2641
• 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
V/D	rs1278982841	-1.75	0.997	D	0.811	0.883	0.938277259092	gnomAD-2.1.1	5.17E-06	None	None	None	None	N	None	0	3.45E-05	None	0	0	None	0	None	0	0	0
V/D	rs1278982841	-1.75	0.997	D	0.811	0.883	0.938277259092	gnomAD-4.0.0	3.47205E-06	None	None	None	None	N	None	0	5.22057E-05	None	0	0	None	0	0	0	0	0
V/F	rs2079162110	None	0.982	D	0.783	0.614	0.915955184925	gnomAD-4.0.0	1.73095E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.10064E-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
V/A	0.7692	likely_pathogenic	0.7754	pathogenic	-1.85	Destabilizing	0.939	D	0.651	neutral	D	0.601105986	None	None	N
V/C	0.9574	likely_pathogenic	0.9515	pathogenic	-1.293	Destabilizing	0.999	D	0.768	deleterious	None	None	None	None	N
V/D	0.9756	likely_pathogenic	0.982	pathogenic	-2.142	Highly Destabilizing	0.997	D	0.811	deleterious	D	0.617962925	None	None	N
V/E	0.9411	likely_pathogenic	0.9502	pathogenic	-2.09	Highly Destabilizing	0.998	D	0.787	deleterious	None	None	None	None	N
V/F	0.5577	ambiguous	0.5681	pathogenic	-1.34	Destabilizing	0.982	D	0.783	deleterious	D	0.617357512	None	None	N
V/G	0.8234	likely_pathogenic	0.8469	pathogenic	-2.217	Highly Destabilizing	0.997	D	0.799	deleterious	D	0.617962925	None	None	N
V/H	0.983	likely_pathogenic	0.9838	pathogenic	-1.794	Destabilizing	0.999	D	0.783	deleterious	None	None	None	None	N
V/I	0.0871	likely_benign	0.0834	benign	-0.9	Destabilizing	0.046	N	0.462	neutral	N	0.503611179	None	None	N
V/K	0.9719	likely_pathogenic	0.9758	pathogenic	-1.481	Destabilizing	0.993	D	0.787	deleterious	None	None	None	None	N
V/L	0.3569	ambiguous	0.3139	benign	-0.9	Destabilizing	0.76	D	0.664	neutral	D	0.599087944	None	None	N
V/M	0.4879	ambiguous	0.4678	ambiguous	-0.753	Destabilizing	0.986	D	0.774	deleterious	None	None	None	None	N
V/N	0.9297	likely_pathogenic	0.9446	pathogenic	-1.402	Destabilizing	0.998	D	0.817	deleterious	None	None	None	None	N
V/P	0.9565	likely_pathogenic	0.9552	pathogenic	-1.186	Destabilizing	0.998	D	0.794	deleterious	None	None	None	None	N
V/Q	0.9557	likely_pathogenic	0.9607	pathogenic	-1.532	Destabilizing	0.998	D	0.797	deleterious	None	None	None	None	N
V/R	0.9545	likely_pathogenic	0.9617	pathogenic	-1.019	Destabilizing	0.998	D	0.815	deleterious	None	None	None	None	N
V/S	0.8878	likely_pathogenic	0.9056	pathogenic	-1.927	Destabilizing	0.993	D	0.777	deleterious	None	None	None	None	N
V/T	0.8174	likely_pathogenic	0.8194	pathogenic	-1.771	Destabilizing	0.953	D	0.745	deleterious	None	None	None	None	N
V/W	0.9852	likely_pathogenic	0.9845	pathogenic	-1.629	Destabilizing	0.999	D	0.748	deleterious	None	None	None	None	N
V/Y	0.9378	likely_pathogenic	0.9374	pathogenic	-1.332	Destabilizing	0.998	D	0.782	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.