TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31349	94270;94271;94272	chr2:178547581;178547580;178547579	chr2:179412308;179412307;179412306
N2AB	29708	89347;89348;89349	chr2:178547581;178547580;178547579	chr2:179412308;179412307;179412306
N2A	28781	86566;86567;86568	chr2:178547581;178547580;178547579	chr2:179412308;179412307;179412306
N2B	22284	67075;67076;67077	chr2:178547581;178547580;178547579	chr2:179412308;179412307;179412306
Novex-1	22409	67450;67451;67452	chr2:178547581;178547580;178547579	chr2:179412308;179412307;179412306
Novex-2	22476	67651;67652;67653	chr2:178547581;178547580;178547579	chr2:179412308;179412307;179412306
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGT
• RefSeq wild type template codon: GCA
• Domain: Fn3-116
• Domain position: 42
• Structural Position: 43
• Q(SASA): 0.3823
• 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
R/C	rs727503549	-2.001	1.0	N	0.845	0.499	0.65667953858	gnomAD-2.1.1	8.93E-05	None	None	None	None	N	None	0	0	None	3.87222E-04	1.02617E-04	None	4.24809E-04	None	1.19894E-04	7.82E-06	2.80899E-04
R/C	rs727503549	-2.001	1.0	N	0.845	0.499	0.65667953858	gnomAD-3.1.2	2.63E-05	None	None	None	None	N	None	0	0	0	0	0	None	9.43E-05	0	1.47E-05	2.07383E-04	4.78011E-04
R/C	rs727503549	-2.001	1.0	N	0.845	0.499	0.65667953858	gnomAD-4.0.0	5.32947E-05	None	None	None	None	N	None	0	0	None	3.71622E-04	2.89842E-04	None	7.81128E-05	0	1.61042E-05	3.73298E-04	6.4043E-05
R/G	rs727503549	-2.66	1.0	N	0.779	0.559	0.629010756219	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
R/H	rs181104321	-2.395	1.0	N	0.715	0.405	None	gnomAD-2.1.1	2.22519E-03	None	None	None	None	N	None	2.76951E-03	7.36002E-04	None	0	0	None	3.27E-05	None	1.41487E-02	1.22756E-03	2.5288E-03
R/H	rs181104321	-2.395	1.0	N	0.715	0.405	None	gnomAD-3.1.2	2.64279E-03	None	None	None	None	N	None	2.99329E-03	1.57377E-03	0	0	0	None	1.51658E-02	0	1.30836E-03	2.07039E-04	1.43403E-03
R/H	rs181104321	-2.395	1.0	N	0.715	0.405	None	1000 genomes	1.19808E-03	None	None	None	None	N	None	8E-04	1.4E-03	None	None	0	4E-03	None	None	None	0	None
R/H	rs181104321	-2.395	1.0	N	0.715	0.405	None	gnomAD-4.0.0	1.71084E-03	None	None	None	None	N	None	2.81243E-03	9.66925E-04	None	0	0	None	1.32006E-02	3.29924E-04	1.32223E-03	1.09789E-04	1.20035E-03
R/L	rs181104321	-1.325	1.0	N	0.779	0.475	0.565757058302	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	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
R/A	0.9698	likely_pathogenic	0.9566	pathogenic	-2.086	Highly Destabilizing	0.999	D	0.627	neutral	None	None	None	None	N
R/C	0.521	ambiguous	0.4975	ambiguous	-2.066	Highly Destabilizing	1.0	D	0.845	deleterious	N	0.514750637	None	None	N
R/D	0.9964	likely_pathogenic	0.9941	pathogenic	-0.787	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
R/E	0.9402	likely_pathogenic	0.9143	pathogenic	-0.62	Destabilizing	0.999	D	0.607	neutral	None	None	None	None	N
R/F	0.9758	likely_pathogenic	0.9673	pathogenic	-1.736	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
R/G	0.9426	likely_pathogenic	0.9167	pathogenic	-2.399	Highly Destabilizing	1.0	D	0.779	deleterious	N	0.508808743	None	None	N
R/H	0.5146	ambiguous	0.504	ambiguous	-2.302	Highly Destabilizing	1.0	D	0.715	prob.delet.	N	0.497959417	None	None	N
R/I	0.9418	likely_pathogenic	0.9268	pathogenic	-1.195	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
R/K	0.2811	likely_benign	0.2501	benign	-1.651	Destabilizing	0.998	D	0.467	neutral	None	None	None	None	N
R/L	0.8767	likely_pathogenic	0.8432	pathogenic	-1.195	Destabilizing	1.0	D	0.779	deleterious	N	0.514057204	None	None	N
R/M	0.8651	likely_pathogenic	0.8185	pathogenic	-1.463	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
R/N	0.9855	likely_pathogenic	0.9792	pathogenic	-1.251	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
R/P	0.9992	likely_pathogenic	0.9987	pathogenic	-1.479	Destabilizing	1.0	D	0.847	deleterious	N	0.509062233	None	None	N
R/Q	0.3208	likely_benign	0.2677	benign	-1.397	Destabilizing	1.0	D	0.698	prob.neutral	None	None	None	None	N
R/S	0.9843	likely_pathogenic	0.9763	pathogenic	-2.309	Highly Destabilizing	1.0	D	0.807	deleterious	D	0.522463256	None	None	N
R/T	0.9625	likely_pathogenic	0.9409	pathogenic	-1.942	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
R/V	0.9477	likely_pathogenic	0.9295	pathogenic	-1.479	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
R/W	0.7864	likely_pathogenic	0.7253	pathogenic	-1.169	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
R/Y	0.9234	likely_pathogenic	0.9034	pathogenic	-0.99	Destabilizing	1.0	D	0.857	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.