TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8949	27070;27071;27072	chr2:178713289;178713288;178713287	chr2:179578016;179578015;179578014
N2AB	8632	26119;26120;26121	chr2:178713289;178713288;178713287	chr2:179578016;179578015;179578014
N2A	7705	23338;23339;23340	chr2:178713289;178713288;178713287	chr2:179578016;179578015;179578014
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-75
• Domain position: 24
• Structural Position: 35
• Q(SASA): 0.1438
• 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/L	rs781692388	-0.509	0.071	D	0.315	0.33	None	gnomAD-2.1.1	1.14E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	2.51E-05	0
V/L	rs781692388	-0.509	0.071	D	0.315	0.33	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
V/L	rs781692388	-0.509	0.071	D	0.315	0.33	None	gnomAD-4.0.0	3.86317E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.19094E-05	0	1.60834E-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
V/A	0.6335	likely_pathogenic	0.6995	pathogenic	-2.151	Highly Destabilizing	0.98	D	0.689	prob.neutral	N	0.517253091	None	None	N
V/C	0.9581	likely_pathogenic	0.9695	pathogenic	-1.856	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
V/D	0.9923	likely_pathogenic	0.9947	pathogenic	-2.319	Highly Destabilizing	0.998	D	0.849	deleterious	D	0.597605669	None	None	N
V/E	0.9813	likely_pathogenic	0.986	pathogenic	-2.129	Highly Destabilizing	0.999	D	0.835	deleterious	None	None	None	None	N
V/F	0.6323	likely_pathogenic	0.671	pathogenic	-1.31	Destabilizing	0.151	N	0.505	neutral	D	0.566152718	None	None	N
V/G	0.775	likely_pathogenic	0.8161	pathogenic	-2.664	Highly Destabilizing	0.998	D	0.843	deleterious	D	0.604338444	None	None	N
V/H	0.994	likely_pathogenic	0.9958	pathogenic	-2.219	Highly Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
V/I	0.1087	likely_benign	0.118	benign	-0.732	Destabilizing	0.835	D	0.644	neutral	N	0.511863127	None	None	N
V/K	0.9892	likely_pathogenic	0.9919	pathogenic	-1.675	Destabilizing	0.999	D	0.831	deleterious	None	None	None	None	N
V/L	0.5279	ambiguous	0.5707	pathogenic	-0.732	Destabilizing	0.071	N	0.315	neutral	D	0.572427227	None	None	N
V/M	0.5675	likely_pathogenic	0.6322	pathogenic	-0.87	Destabilizing	0.991	D	0.727	prob.delet.	None	None	None	None	N
V/N	0.9761	likely_pathogenic	0.9834	pathogenic	-1.908	Destabilizing	0.999	D	0.844	deleterious	None	None	None	None	N
V/P	0.9881	likely_pathogenic	0.99	pathogenic	-1.177	Destabilizing	0.999	D	0.822	deleterious	None	None	None	None	N
V/Q	0.9822	likely_pathogenic	0.9856	pathogenic	-1.805	Destabilizing	0.999	D	0.823	deleterious	None	None	None	None	N
V/R	0.9754	likely_pathogenic	0.9803	pathogenic	-1.454	Destabilizing	0.999	D	0.842	deleterious	None	None	None	None	N
V/S	0.892	likely_pathogenic	0.924	pathogenic	-2.619	Highly Destabilizing	0.999	D	0.824	deleterious	None	None	None	None	N
V/T	0.7957	likely_pathogenic	0.8405	pathogenic	-2.284	Highly Destabilizing	0.985	D	0.7	prob.neutral	None	None	None	None	N
V/W	0.991	likely_pathogenic	0.9931	pathogenic	-1.688	Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
V/Y	0.9486	likely_pathogenic	0.9582	pathogenic	-1.359	Destabilizing	0.983	D	0.821	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.