TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22170	66733;66734;66735	chr2:178581760;178581759;178581758	chr2:179446487;179446486;179446485
N2AB	20529	61810;61811;61812	chr2:178581760;178581759;178581758	chr2:179446487;179446486;179446485
N2A	19602	59029;59030;59031	chr2:178581760;178581759;178581758	chr2:179446487;179446486;179446485
N2B	13105	39538;39539;39540	chr2:178581760;178581759;178581758	chr2:179446487;179446486;179446485
Novex-1	13230	39913;39914;39915	chr2:178581760;178581759;178581758	chr2:179446487;179446486;179446485
Novex-2	13297	40114;40115;40116	chr2:178581760;178581759;178581758	chr2:179446487;179446486;179446485
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGC
• RefSeq wild type template codon: GCG
• Domain: Fn3-49
• Domain position: 15
• Structural Position: 17
• Q(SASA): 0.4898
• 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	rs377642110	-0.491	0.995	N	0.438	0.271	None	gnomAD-2.1.1	1.28E-05	None	None	None	None	N	None	2.08855E-04	0	None	0	0	None	0	None	0	0	0
R/C	rs377642110	-0.491	0.995	N	0.438	0.271	None	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	7.24E-05	0	0	0	0	None	0	0	0	0	0
R/C	rs377642110	-0.491	0.995	N	0.438	0.271	None	gnomAD-4.0.0	8.09714E-06	None	None	None	None	N	None	6.69344E-05	0	None	0	0	None	0	0	5.9547E-06	0	1.60999E-05
R/G	None	None	0.549	N	0.429	0.164	0.359557344763	gnomAD-4.0.0	6.88022E-07	None	None	None	None	N	None	0	0	None	0	2.55637E-05	None	0	0	0	0	0
R/H	rs190711640	-1.148	0.008	N	0.108	0.06	None	gnomAD-2.1.1	4.26E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.48E-06	0
R/H	rs190711640	-1.148	0.008	N	0.108	0.06	None	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	1.94175E-04	None	0	0	0	0	0
R/H	rs190711640	-1.148	0.008	N	0.108	0.06	None	gnomAD-4.0.0	7.47543E-06	None	None	None	None	N	None	0	0	None	0	2.2603E-05	None	0	0	8.50781E-06	0	1.60953E-05
R/L	rs190711640	None	0.549	N	0.403	0.135	0.317084106153	gnomAD-4.0.0	7.5697E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.03E-06	0	1.66606E-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	0.5294	ambiguous	0.5474	ambiguous	-0.201	Destabilizing	0.116	N	0.384	neutral	None	None	None	None	N
R/C	0.2014	likely_benign	0.2285	benign	-0.162	Destabilizing	0.995	D	0.438	neutral	N	0.48297858	None	None	N
R/D	0.8369	likely_pathogenic	0.8512	pathogenic	-0.119	Destabilizing	0.388	N	0.417	neutral	None	None	None	None	N
R/E	0.6224	likely_pathogenic	0.6399	pathogenic	-0.065	Destabilizing	0.116	N	0.324	neutral	None	None	None	None	N
R/F	0.7517	likely_pathogenic	0.7958	pathogenic	-0.456	Destabilizing	0.69	D	0.451	neutral	None	None	None	None	N
R/G	0.4124	ambiguous	0.4289	ambiguous	-0.4	Destabilizing	0.549	D	0.429	neutral	N	0.474034591	None	None	N
R/H	0.1054	likely_benign	0.1279	benign	-0.853	Destabilizing	0.008	N	0.108	neutral	N	0.474266665	None	None	N
R/I	0.585	likely_pathogenic	0.5894	pathogenic	0.29	Stabilizing	0.818	D	0.454	neutral	None	None	None	None	N
R/K	0.1183	likely_benign	0.1233	benign	-0.187	Destabilizing	0.001	N	0.103	neutral	None	None	None	None	N
R/L	0.439	ambiguous	0.4622	ambiguous	0.29	Stabilizing	0.549	D	0.403	neutral	N	0.467240955	None	None	N
R/M	0.5572	ambiguous	0.562	ambiguous	0.074	Stabilizing	0.932	D	0.387	neutral	None	None	None	None	N
R/N	0.655	likely_pathogenic	0.6949	pathogenic	0.222	Stabilizing	0.241	N	0.287	neutral	None	None	None	None	N
R/P	0.725	likely_pathogenic	0.7272	pathogenic	0.147	Stabilizing	0.896	D	0.421	neutral	N	0.453947321	None	None	N
R/Q	0.1571	likely_benign	0.1671	benign	0.004	Stabilizing	0.388	N	0.372	neutral	None	None	None	None	N
R/S	0.6182	likely_pathogenic	0.643	pathogenic	-0.252	Destabilizing	0.549	D	0.37	neutral	N	0.396744457	None	None	N
R/T	0.5075	ambiguous	0.5193	ambiguous	-0.065	Destabilizing	0.388	N	0.379	neutral	None	None	None	None	N
R/V	0.6175	likely_pathogenic	0.635	pathogenic	0.147	Stabilizing	0.69	D	0.433	neutral	None	None	None	None	N
R/W	0.4212	ambiguous	0.4533	ambiguous	-0.418	Destabilizing	0.981	D	0.507	neutral	None	None	None	None	N
R/Y	0.5208	ambiguous	0.5903	pathogenic	-0.02	Destabilizing	0.527	D	0.417	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.