TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23624	71095;71096;71097	chr2:178575262;178575261;178575260	chr2:179439989;179439988;179439987
N2AB	21983	66172;66173;66174	chr2:178575262;178575261;178575260	chr2:179439989;179439988;179439987
N2A	21056	63391;63392;63393	chr2:178575262;178575261;178575260	chr2:179439989;179439988;179439987
N2B	14559	43900;43901;43902	chr2:178575262;178575261;178575260	chr2:179439989;179439988;179439987
Novex-1	14684	44275;44276;44277	chr2:178575262;178575261;178575260	chr2:179439989;179439988;179439987
Novex-2	14751	44476;44477;44478	chr2:178575262;178575261;178575260	chr2:179439989;179439988;179439987
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: Fn3-59
• Domain position: 93
• Structural Position: 130
• Q(SASA): 0.0531
• 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/A	None	None	0.622	N	0.497	0.297	0.418344901717	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
V/L	rs761395692	-1.481	0.264	N	0.423	0.088	0.284150004643	gnomAD-2.1.1	2.02E-05	None	None	None	None	N	None	0	0	None	0	0	None	1.6357E-04	None	0	0	0
V/L	rs761395692	-1.481	0.264	N	0.423	0.088	0.284150004643	gnomAD-4.0.0	1.02662E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.73937E-04	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	0.6379	likely_pathogenic	0.5741	pathogenic	-2.446	Highly Destabilizing	0.622	D	0.497	neutral	N	0.385010097	None	None	N
V/C	0.927	likely_pathogenic	0.9092	pathogenic	-2.266	Highly Destabilizing	0.998	D	0.663	prob.neutral	None	None	None	None	N
V/D	0.9974	likely_pathogenic	0.9964	pathogenic	-3.212	Highly Destabilizing	0.989	D	0.781	deleterious	N	0.477619301	None	None	N
V/E	0.9909	likely_pathogenic	0.9885	pathogenic	-2.944	Highly Destabilizing	0.991	D	0.717	prob.delet.	None	None	None	None	N
V/F	0.9121	likely_pathogenic	0.8784	pathogenic	-1.339	Destabilizing	0.933	D	0.647	neutral	N	0.477112322	None	None	N
V/G	0.9117	likely_pathogenic	0.8826	pathogenic	-2.991	Highly Destabilizing	0.989	D	0.761	deleterious	N	0.477619301	None	None	N
V/H	0.9973	likely_pathogenic	0.9966	pathogenic	-2.634	Highly Destabilizing	0.998	D	0.775	deleterious	None	None	None	None	N
V/I	0.0984	likely_benign	0.0968	benign	-0.88	Destabilizing	0.005	N	0.203	neutral	N	0.418794597	None	None	N
V/K	0.9928	likely_pathogenic	0.9915	pathogenic	-1.84	Destabilizing	0.974	D	0.723	deleterious	None	None	None	None	N
V/L	0.6746	likely_pathogenic	0.6185	pathogenic	-0.88	Destabilizing	0.264	N	0.423	neutral	N	0.483902081	None	None	N
V/M	0.7603	likely_pathogenic	0.6935	pathogenic	-1.351	Destabilizing	0.949	D	0.564	neutral	None	None	None	None	N
V/N	0.9857	likely_pathogenic	0.9798	pathogenic	-2.371	Highly Destabilizing	0.991	D	0.774	deleterious	None	None	None	None	N
V/P	0.9223	likely_pathogenic	0.9134	pathogenic	-1.382	Destabilizing	0.991	D	0.689	prob.delet.	None	None	None	None	N
V/Q	0.987	likely_pathogenic	0.9824	pathogenic	-2.122	Highly Destabilizing	0.991	D	0.709	prob.delet.	None	None	None	None	N
V/R	0.9809	likely_pathogenic	0.9779	pathogenic	-1.799	Destabilizing	0.991	D	0.774	deleterious	None	None	None	None	N
V/S	0.8993	likely_pathogenic	0.8718	pathogenic	-2.944	Highly Destabilizing	0.974	D	0.647	neutral	None	None	None	None	N
V/T	0.8091	likely_pathogenic	0.7911	pathogenic	-2.529	Highly Destabilizing	0.841	D	0.577	neutral	None	None	None	None	N
V/W	0.9985	likely_pathogenic	0.998	pathogenic	-1.79	Destabilizing	0.998	D	0.724	deleterious	None	None	None	None	N
V/Y	0.9941	likely_pathogenic	0.992	pathogenic	-1.524	Destabilizing	0.991	D	0.634	neutral	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.