TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18349	55270;55271;55272	chr2:178602357;178602356;178602355	chr2:179467084;179467083;179467082
N2AB	16708	50347;50348;50349	chr2:178602357;178602356;178602355	chr2:179467084;179467083;179467082
N2A	15781	47566;47567;47568	chr2:178602357;178602356;178602355	chr2:179467084;179467083;179467082
N2B	9284	28075;28076;28077	chr2:178602357;178602356;178602355	chr2:179467084;179467083;179467082
Novex-1	9409	28450;28451;28452	chr2:178602357;178602356;178602355	chr2:179467084;179467083;179467082
Novex-2	9476	28651;28652;28653	chr2:178602357;178602356;178602355	chr2:179467084;179467083;179467082
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Fn3-21
• Domain position: 78
• Structural Position: 108
• Q(SASA): 0.1193
• 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/G	rs772880269	-3.586	0.999	D	0.825	0.88	0.910249762803	gnomAD-2.1.1	8.06E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	1.66279E-04
V/G	rs772880269	-3.586	0.999	D	0.825	0.88	0.910249762803	gnomAD-4.0.0	2.05371E-06	None	None	None	None	N	None	0	2.23904E-05	None	0	0	None	0	0	8.998E-07	0	1.65782E-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	0.9144	likely_pathogenic	0.9097	pathogenic	-2.609	Highly Destabilizing	0.948	D	0.6	neutral	D	0.547377333	None	None	N
V/C	0.9346	likely_pathogenic	0.9531	pathogenic	-2.199	Highly Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
V/D	0.9974	likely_pathogenic	0.9967	pathogenic	-3.472	Highly Destabilizing	0.999	D	0.848	deleterious	None	None	None	None	N
V/E	0.9908	likely_pathogenic	0.9884	pathogenic	-3.186	Highly Destabilizing	0.999	D	0.808	deleterious	D	0.638305922	None	None	N
V/F	0.863	likely_pathogenic	0.8805	pathogenic	-1.331	Destabilizing	0.998	D	0.702	prob.neutral	None	None	None	None	N
V/G	0.9117	likely_pathogenic	0.9	pathogenic	-3.158	Highly Destabilizing	0.999	D	0.825	deleterious	D	0.638305923	None	None	N
V/H	0.9973	likely_pathogenic	0.9972	pathogenic	-2.875	Highly Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
V/I	0.0985	likely_benign	0.1059	benign	-1.01	Destabilizing	0.246	N	0.192	neutral	None	None	None	None	N
V/K	0.9921	likely_pathogenic	0.9896	pathogenic	-2.061	Highly Destabilizing	0.999	D	0.808	deleterious	None	None	None	None	N
V/L	0.6126	likely_pathogenic	0.7039	pathogenic	-1.01	Destabilizing	0.9	D	0.289	neutral	N	0.511885931	None	None	N
V/M	0.7369	likely_pathogenic	0.7874	pathogenic	-1.401	Destabilizing	0.997	D	0.61	neutral	D	0.551416258	None	None	N
V/N	0.9895	likely_pathogenic	0.9887	pathogenic	-2.647	Highly Destabilizing	0.999	D	0.857	deleterious	None	None	None	None	N
V/P	0.9944	likely_pathogenic	0.9937	pathogenic	-1.527	Destabilizing	0.999	D	0.823	deleterious	None	None	None	None	N
V/Q	0.9885	likely_pathogenic	0.987	pathogenic	-2.336	Highly Destabilizing	0.999	D	0.847	deleterious	None	None	None	None	N
V/R	0.9841	likely_pathogenic	0.9803	pathogenic	-2.026	Highly Destabilizing	0.999	D	0.86	deleterious	None	None	None	None	N
V/S	0.9721	likely_pathogenic	0.9659	pathogenic	-3.148	Highly Destabilizing	0.999	D	0.768	deleterious	None	None	None	None	N
V/T	0.9351	likely_pathogenic	0.9266	pathogenic	-2.725	Highly Destabilizing	0.992	D	0.603	neutral	None	None	None	None	N
V/W	0.9959	likely_pathogenic	0.9965	pathogenic	-1.877	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
V/Y	0.9848	likely_pathogenic	0.9871	pathogenic	-1.662	Destabilizing	0.999	D	0.696	prob.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.