TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2868	8827;8828;8829	chr2:178770099;178770098;178770097	chr2:179634826;179634825;179634824
N2AB	2868	8827;8828;8829	chr2:178770099;178770098;178770097	chr2:179634826;179634825;179634824
N2A	2868	8827;8828;8829	chr2:178770099;178770098;178770097	chr2:179634826;179634825;179634824
N2B	2822	8689;8690;8691	chr2:178770099;178770098;178770097	chr2:179634826;179634825;179634824
Novex-1	2822	8689;8690;8691	chr2:178770099;178770098;178770097	chr2:179634826;179634825;179634824
Novex-2	2822	8689;8690;8691	chr2:178770099;178770098;178770097	chr2:179634826;179634825;179634824
Novex-3	2868	8827;8828;8829	chr2:178770099;178770098;178770097	chr2:179634826;179634825;179634824

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-18
• Domain position: 74
• Structural Position: 158
• Q(SASA): 0.1815
• 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	rs765207321	-2.208	0.543	N	0.321	0.342	0.552245614029	gnomAD-2.1.1	3.98E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
V/A	rs765207321	-2.208	0.543	N	0.321	0.342	0.552245614029	gnomAD-4.0.0	3.18094E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85644E-06	1.43271E-05	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	0.3428	ambiguous	0.4352	ambiguous	-1.725	Destabilizing	0.543	D	0.321	neutral	N	0.455563842	None	None	N
V/C	0.8999	likely_pathogenic	0.9448	pathogenic	-1.302	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
V/D	0.9852	likely_pathogenic	0.9899	pathogenic	-1.941	Destabilizing	0.998	D	0.869	deleterious	D	0.66522019	None	None	N
V/E	0.9762	likely_pathogenic	0.982	pathogenic	-1.801	Destabilizing	0.999	D	0.849	deleterious	None	None	None	None	N
V/F	0.6265	likely_pathogenic	0.7088	pathogenic	-1.007	Destabilizing	0.999	D	0.832	deleterious	D	0.584681827	None	None	N
V/G	0.7997	likely_pathogenic	0.8596	pathogenic	-2.194	Highly Destabilizing	0.997	D	0.797	deleterious	D	0.551495101	None	None	N
V/H	0.9866	likely_pathogenic	0.9913	pathogenic	-1.95	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
V/I	0.1033	likely_benign	0.1105	benign	-0.468	Destabilizing	0.987	D	0.589	neutral	D	0.522962527	None	None	N
V/K	0.9854	likely_pathogenic	0.9879	pathogenic	-1.665	Destabilizing	0.999	D	0.847	deleterious	None	None	None	None	N
V/L	0.5442	ambiguous	0.6451	pathogenic	-0.468	Destabilizing	0.973	D	0.651	neutral	D	0.522807719	None	None	N
V/M	0.5348	ambiguous	0.6513	pathogenic	-0.453	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
V/N	0.9656	likely_pathogenic	0.9783	pathogenic	-1.724	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
V/P	0.9809	likely_pathogenic	0.9852	pathogenic	-0.855	Destabilizing	0.999	D	0.861	deleterious	None	None	None	None	N
V/Q	0.9719	likely_pathogenic	0.9804	pathogenic	-1.661	Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
V/R	0.9676	likely_pathogenic	0.9736	pathogenic	-1.403	Destabilizing	0.999	D	0.854	deleterious	None	None	None	None	N
V/S	0.7494	likely_pathogenic	0.8177	pathogenic	-2.309	Highly Destabilizing	0.995	D	0.813	deleterious	None	None	None	None	N
V/T	0.5126	ambiguous	0.5968	pathogenic	-2.035	Highly Destabilizing	0.992	D	0.647	neutral	None	None	None	None	N
V/W	0.9877	likely_pathogenic	0.9924	pathogenic	-1.442	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
V/Y	0.9624	likely_pathogenic	0.9745	pathogenic	-1.067	Destabilizing	1.0	D	0.819	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.