TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22233	66922;66923;66924	chr2:178581571;178581570;178581569	chr2:179446298;179446297;179446296
N2AB	20592	61999;62000;62001	chr2:178581571;178581570;178581569	chr2:179446298;179446297;179446296
N2A	19665	59218;59219;59220	chr2:178581571;178581570;178581569	chr2:179446298;179446297;179446296
N2B	13168	39727;39728;39729	chr2:178581571;178581570;178581569	chr2:179446298;179446297;179446296
Novex-1	13293	40102;40103;40104	chr2:178581571;178581570;178581569	chr2:179446298;179446297;179446296
Novex-2	13360	40303;40304;40305	chr2:178581571;178581570;178581569	chr2:179446298;179446297;179446296
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-49
• Domain position: 78
• Structural Position: 109
• Q(SASA): 0.0927
• 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
Y/C	rs763250975	-1.433	None	N	0.452	0.308	0.234412748748	gnomAD-2.1.1	8.07E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
Y/C	rs763250975	-1.433	None	N	0.452	0.308	0.234412748748	gnomAD-4.0.0	3.18792E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.72597E-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
Y/A	0.4588	ambiguous	0.5123	ambiguous	-3.325	Highly Destabilizing	0.002	N	0.561	neutral	None	None	None	None	N
Y/C	0.1014	likely_benign	0.1107	benign	-1.765	Destabilizing	None	N	0.452	neutral	N	0.379684422	None	None	N
Y/D	0.7768	likely_pathogenic	0.8435	pathogenic	-3.156	Highly Destabilizing	0.033	N	0.658	neutral	N	0.46732986	None	None	N
Y/E	0.855	likely_pathogenic	0.8834	pathogenic	-2.983	Highly Destabilizing	0.018	N	0.619	neutral	None	None	None	None	N
Y/F	0.0987	likely_benign	0.1021	benign	-1.274	Destabilizing	None	N	0.245	neutral	N	0.412026127	None	None	N
Y/G	0.6088	likely_pathogenic	0.6637	pathogenic	-3.706	Highly Destabilizing	0.009	N	0.609	neutral	None	None	None	None	N
Y/H	0.2194	likely_benign	0.2636	benign	-2.08	Highly Destabilizing	0.427	N	0.599	neutral	N	0.4843103	None	None	N
Y/I	0.4268	ambiguous	0.4756	ambiguous	-2.065	Highly Destabilizing	None	N	0.37	neutral	None	None	None	None	N
Y/K	0.6009	likely_pathogenic	0.6576	pathogenic	-2.107	Highly Destabilizing	0.018	N	0.613	neutral	None	None	None	None	N
Y/L	0.3702	ambiguous	0.4308	ambiguous	-2.065	Highly Destabilizing	None	N	0.345	neutral	None	None	None	None	N
Y/M	0.4443	ambiguous	0.5112	ambiguous	-1.725	Destabilizing	0.138	N	0.661	neutral	None	None	None	None	N
Y/N	0.3634	ambiguous	0.4366	ambiguous	-2.698	Highly Destabilizing	0.033	N	0.651	neutral	N	0.4843103	None	None	N
Y/P	0.9904	likely_pathogenic	0.9942	pathogenic	-2.497	Highly Destabilizing	0.085	N	0.641	neutral	None	None	None	None	N
Y/Q	0.5796	likely_pathogenic	0.6371	pathogenic	-2.557	Highly Destabilizing	0.085	N	0.666	neutral	None	None	None	None	N
Y/R	0.4159	ambiguous	0.4657	ambiguous	-1.673	Destabilizing	0.044	N	0.64	neutral	None	None	None	None	N
Y/S	0.2031	likely_benign	0.244	benign	-3.122	Highly Destabilizing	None	N	0.422	neutral	N	0.373430454	None	None	N
Y/T	0.2784	likely_benign	0.3957	ambiguous	-2.844	Highly Destabilizing	None	N	0.445	neutral	None	None	None	None	N
Y/V	0.3205	likely_benign	0.381	ambiguous	-2.497	Highly Destabilizing	0.004	N	0.507	neutral	None	None	None	None	N
Y/W	0.4628	ambiguous	0.4943	ambiguous	-0.553	Destabilizing	0.245	N	0.632	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.