TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3148	9667;9668;9669	chr2:178767788;178767787;178767786	chr2:179632515;179632514;179632513
N2AB	3148	9667;9668;9669	chr2:178767788;178767787;178767786	chr2:179632515;179632514;179632513
N2A	3148	9667;9668;9669	chr2:178767788;178767787;178767786	chr2:179632515;179632514;179632513
N2B	3102	9529;9530;9531	chr2:178767788;178767787;178767786	chr2:179632515;179632514;179632513
Novex-1	3102	9529;9530;9531	chr2:178767788;178767787;178767786	chr2:179632515;179632514;179632513
Novex-2	3102	9529;9530;9531	chr2:178767788;178767787;178767786	chr2:179632515;179632514;179632513
Novex-3	3148	9667;9668;9669	chr2:178767788;178767787;178767786	chr2:179632515;179632514;179632513

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGC
• RefSeq wild type template codon: GCG
• Domain: Ig-22
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.6655
• 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	rs372196051	-0.235	1.0	N	0.761	0.331	None	gnomAD-2.1.1	1.77E-05	None	None	None	None	N	None	0	2.82E-05	None	0	0	None	0	None	0	3.11E-05	0
R/C	rs372196051	-0.235	1.0	N	0.761	0.331	None	gnomAD-3.1.2	2.63E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	5.88E-05	0	0
R/C	rs372196051	-0.235	1.0	N	0.761	0.331	None	gnomAD-4.0.0	3.65561E-05	None	None	None	None	N	None	0	1.66661E-05	None	0	0	None	0	0	4.83054E-05	0	1.60046E-05
R/H	rs368786036	-0.944	1.0	N	0.764	0.267	None	gnomAD-2.1.1	2.79E-05	None	None	None	None	N	None	6.15E-05	0	None	0	0	None	1.30659E-04	None	0	1.76E-05	0
R/H	rs368786036	-0.944	1.0	N	0.764	0.267	None	gnomAD-3.1.2	5.26E-05	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	8.82E-05	2.07211E-04	0
R/H	rs368786036	-0.944	1.0	N	0.764	0.267	None	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	0	None	None	0	0	None	None	None	1E-03	None
R/H	rs368786036	-0.944	1.0	N	0.764	0.267	None	gnomAD-4.0.0	5.6378E-05	None	None	None	None	N	None	5.32992E-05	0	None	0	2.22797E-05	None	0	0	6.44067E-05	7.68555E-05	4.79954E-05
R/L	rs368786036	0.416	1.0	N	0.624	0.284	0.254761474806	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
R/L	rs368786036	0.416	1.0	N	0.624	0.284	0.254761474806	gnomAD-4.0.0	8.20898E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.5972E-06	3.47794E-05	8.27897E-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
R/A	0.8631	likely_pathogenic	0.7703	pathogenic	0.082	Stabilizing	0.999	D	0.658	neutral	None	None	None	None	N
R/C	0.6248	likely_pathogenic	0.4441	ambiguous	-0.092	Destabilizing	1.0	D	0.761	deleterious	N	0.341993683	None	None	N
R/D	0.9603	likely_pathogenic	0.914	pathogenic	-0.196	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
R/E	0.8277	likely_pathogenic	0.7333	pathogenic	-0.141	Destabilizing	0.999	D	0.709	prob.delet.	None	None	None	None	N
R/F	0.8772	likely_pathogenic	0.8111	pathogenic	-0.158	Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	N
R/G	0.8118	likely_pathogenic	0.6817	pathogenic	-0.095	Destabilizing	1.0	D	0.624	neutral	N	0.341050084	None	None	N
R/H	0.2607	likely_benign	0.1623	benign	-0.615	Destabilizing	1.0	D	0.764	deleterious	N	0.344364775	None	None	N
R/I	0.7028	likely_pathogenic	0.6024	pathogenic	0.508	Stabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
R/K	0.2604	likely_benign	0.2066	benign	-0.039	Destabilizing	0.998	D	0.649	neutral	None	None	None	None	N
R/L	0.6255	likely_pathogenic	0.5304	ambiguous	0.508	Stabilizing	1.0	D	0.624	neutral	N	0.336827851	None	None	N
R/M	0.7542	likely_pathogenic	0.6613	pathogenic	0.051	Stabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
R/N	0.9003	likely_pathogenic	0.8073	pathogenic	0.141	Stabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
R/P	0.9632	likely_pathogenic	0.9237	pathogenic	0.385	Stabilizing	1.0	D	0.694	prob.neutral	N	0.337254512	None	None	N
R/Q	0.2969	likely_benign	0.2119	benign	0.071	Stabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
R/S	0.9045	likely_pathogenic	0.8131	pathogenic	-0.104	Destabilizing	1.0	D	0.673	neutral	N	0.339854219	None	None	N
R/T	0.7675	likely_pathogenic	0.6343	pathogenic	0.074	Stabilizing	1.0	D	0.673	neutral	None	None	None	None	N
R/V	0.7637	likely_pathogenic	0.6521	pathogenic	0.385	Stabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
R/W	0.5191	ambiguous	0.4215	ambiguous	-0.278	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
R/Y	0.7791	likely_pathogenic	0.653	pathogenic	0.132	Stabilizing	1.0	D	0.722	prob.delet.	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.