TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31852	95779;95780;95781	chr2:178545556;178545555;178545554	chr2:179410283;179410282;179410281
N2AB	30211	90856;90857;90858	chr2:178545556;178545555;178545554	chr2:179410283;179410282;179410281
N2A	29284	88075;88076;88077	chr2:178545556;178545555;178545554	chr2:179410283;179410282;179410281
N2B	22787	68584;68585;68586	chr2:178545556;178545555;178545554	chr2:179410283;179410282;179410281
Novex-1	22912	68959;68960;68961	chr2:178545556;178545555;178545554	chr2:179410283;179410282;179410281
Novex-2	22979	69160;69161;69162	chr2:178545556;178545555;178545554	chr2:179410283;179410282;179410281
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Fn3-120
• Domain position: 46
• Structural Position: 63
• Q(SASA): 1.042
• Predicted PPI site: I

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
L/P	rs62621206	-0.064	0.896	N	0.319	0.2	None	gnomAD-2.1.1	1.08384E-02	None	None	None	None	I	None	3.01853E-03	5.59765E-03	None	9.08564E-03	0	None	2.64689E-03	None	1.23891E-02	1.70026E-02	1.4446E-02
L/P	rs62621206	-0.064	0.896	N	0.319	0.2	None	gnomAD-3.1.2	1.12135E-02	None	None	None	None	I	None	3.13707E-03	1.1261E-02	3.95604E-02	1.18088E-02	0	None	1.03715E-02	0	1.72738E-02	2.28311E-03	1.48325E-02
L/P	rs62621206	-0.064	0.896	N	0.319	0.2	None	1000 genomes	5.59105E-03	None	None	None	None	I	None	8E-04	8.6E-03	None	None	0	1.99E-02	None	None	None	1E-03	None
L/P	rs62621206	-0.064	0.896	N	0.319	0.2	None	gnomAD-4.0.0	1.51072E-02	None	None	None	None	I	None	2.85227E-03	8.09838E-03	None	9.62903E-03	4.45732E-05	None	1.25922E-02	1.37054E-02	1.80035E-02	2.81102E-03	1.5559E-02
L/Q	None	-0.05	0.81	N	0.304	0.18	0.40146981186	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
L/Q	None	-0.05	0.81	N	0.304	0.18	0.40146981186	gnomAD-4.0.0	1.36847E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99523E-07	1.15934E-05	0
L/R	rs62621206	0.315	0.81	N	0.311	0.204	0.372087925617	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	0	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
L/A	0.2317	likely_benign	0.2581	benign	-0.435	Destabilizing	0.25	N	0.365	neutral	None	None	None	None	I
L/C	0.5374	ambiguous	0.6068	pathogenic	-0.867	Destabilizing	0.992	D	0.294	neutral	None	None	None	None	I
L/D	0.7487	likely_pathogenic	0.8146	pathogenic	0.026	Stabilizing	0.85	D	0.322	neutral	None	None	None	None	I
L/E	0.49	ambiguous	0.5704	pathogenic	-0.057	Destabilizing	0.617	D	0.319	neutral	None	None	None	None	I
L/F	0.1706	likely_benign	0.186	benign	-0.559	Destabilizing	0.92	D	0.288	neutral	None	None	None	None	I
L/G	0.4441	ambiguous	0.4962	ambiguous	-0.526	Destabilizing	0.447	N	0.34	neutral	None	None	None	None	I
L/H	0.3109	likely_benign	0.3499	ambiguous	0.092	Stabilizing	0.977	D	0.287	neutral	None	None	None	None	I
L/I	0.0927	likely_benign	0.0984	benign	-0.31	Destabilizing	0.021	N	0.202	neutral	None	None	None	None	I
L/K	0.3908	ambiguous	0.4605	ambiguous	-0.299	Destabilizing	0.447	N	0.3	neutral	None	None	None	None	I
L/M	0.1049	likely_benign	0.1093	benign	-0.61	Destabilizing	0.896	D	0.291	neutral	N	0.474440023	None	None	I
L/N	0.3269	likely_benign	0.3863	ambiguous	-0.199	Destabilizing	0.739	D	0.316	neutral	None	None	None	None	I
L/P	0.2839	likely_benign	0.2866	benign	-0.325	Destabilizing	0.896	D	0.319	neutral	N	0.490812198	None	None	I
L/Q	0.1847	likely_benign	0.2019	benign	-0.333	Destabilizing	0.81	D	0.304	neutral	N	0.454024678	None	None	I
L/R	0.3253	likely_benign	0.3687	ambiguous	0.098	Stabilizing	0.81	D	0.311	neutral	N	0.493025784	None	None	I
L/S	0.2449	likely_benign	0.2706	benign	-0.625	Destabilizing	0.021	N	0.321	neutral	None	None	None	None	I
L/T	0.1898	likely_benign	0.216	benign	-0.607	Destabilizing	0.009	N	0.173	neutral	None	None	None	None	I
L/V	0.0882	likely_benign	0.0944	benign	-0.325	Destabilizing	0.002	N	0.126	neutral	N	0.449312292	None	None	I
L/W	0.3294	likely_benign	0.3551	ambiguous	-0.574	Destabilizing	0.992	D	0.331	neutral	None	None	None	None	I
L/Y	0.4081	ambiguous	0.4519	ambiguous	-0.353	Destabilizing	0.972	D	0.297	neutral	None	None	None	None	I

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.