TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16186	48781;48782;48783	chr2:178615389;178615388;178615387	chr2:179480116;179480115;179480114
N2AB	14545	43858;43859;43860	chr2:178615389;178615388;178615387	chr2:179480116;179480115;179480114
N2A	13618	41077;41078;41079	chr2:178615389;178615388;178615387	chr2:179480116;179480115;179480114
N2B	7121	21586;21587;21588	chr2:178615389;178615388;178615387	chr2:179480116;179480115;179480114
Novex-1	7246	21961;21962;21963	chr2:178615389;178615388;178615387	chr2:179480116;179480115;179480114
Novex-2	7313	22162;22163;22164	chr2:178615389;178615388;178615387	chr2:179480116;179480115;179480114
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: Fn3-5
• Domain position: 32
• Structural Position: 34
• Q(SASA): 0.7491
• 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
R/C	rs377563403	-0.044	1.0	N	0.445	0.396	0.556145022309	gnomAD-2.1.1	8.46E-05	None	None	None	None	I	None	1.2945E-04	2.9E-05	None	0	0	None	5.23115E-04	None	0	1.78E-05	0
R/C	rs377563403	-0.044	1.0	N	0.445	0.396	0.556145022309	gnomAD-3.1.2	3.95E-05	None	None	None	None	I	None	9.67E-05	0	0	0	0	None	0	0	0	4.14766E-04	0
R/C	rs377563403	-0.044	1.0	N	0.445	0.396	0.556145022309	gnomAD-4.0.0	3.59688E-05	None	None	None	None	I	None	6.67735E-05	0	None	0	0	None	0	0	8.48151E-06	4.72413E-04	0
R/H	rs769784536	-0.687	0.999	N	0.437	0.288	0.233150807113	gnomAD-2.1.1	2.01E-05	None	None	None	None	I	None	0	0	None	0	0	None	6.54E-05	None	0	1.78E-05	1.66279E-04
R/H	rs769784536	-0.687	0.999	N	0.437	0.288	0.233150807113	gnomAD-3.1.2	2.63E-05	None	None	None	None	I	None	2.42E-05	0	0	0	0	None	9.42E-05	0	0	4.1511E-04	0
R/H	rs769784536	-0.687	0.999	N	0.437	0.288	0.233150807113	gnomAD-4.0.0	2.17058E-05	None	None	None	None	I	None	1.33715E-05	0	None	0	0	None	1.56206E-05	0	2.03551E-05	8.78908E-05	1.60272E-05
R/L	rs769784536	0.531	0.983	N	0.56	0.276	0.515317749148	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	5.59E-05	None	0	None	0	0	0
R/L	rs769784536	0.531	0.983	N	0.56	0.276	0.515317749148	gnomAD-3.1.2	1.98E-05	None	None	None	None	I	None	0	1.97006E-04	0	0	0	None	0	0	0	0	0
R/L	rs769784536	0.531	0.983	N	0.56	0.276	0.515317749148	gnomAD-4.0.0	6.20167E-06	None	None	None	None	I	None	0	5.00734E-05	None	0	2.23484E-05	None	0	0	2.54439E-06	0	4.80815E-05
R/S	rs377563403	None	0.533	N	0.22	0.136	None	gnomAD-3.1.2	6.59E-06	None	None	None	None	I	None	2.42E-05	0	0	0	0	None	0	0	0	0	0
R/S	rs377563403	None	0.533	N	0.22	0.136	None	gnomAD-4.0.0	1.86059E-06	None	None	None	None	I	None	2.6753E-05	0	None	0	0	None	0	0	8.48145E-07	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
R/A	0.3735	ambiguous	0.278	benign	0.099	Stabilizing	0.759	D	0.442	neutral	None	None	None	None	I
R/C	0.2486	likely_benign	0.1942	benign	-0.152	Destabilizing	1.0	D	0.445	neutral	N	0.476369479	None	None	I
R/D	0.741	likely_pathogenic	0.6231	pathogenic	-0.246	Destabilizing	0.939	D	0.557	neutral	None	None	None	None	I
R/E	0.4922	ambiguous	0.3903	ambiguous	-0.192	Destabilizing	0.939	D	0.391	neutral	None	None	None	None	I
R/F	0.5992	likely_pathogenic	0.501	ambiguous	-0.189	Destabilizing	0.997	D	0.475	neutral	None	None	None	None	I
R/G	0.3334	likely_benign	0.239	benign	-0.062	Destabilizing	0.037	N	0.211	neutral	N	0.443055437	None	None	I
R/H	0.1344	likely_benign	0.1133	benign	-0.624	Destabilizing	0.999	D	0.437	neutral	N	0.478736212	None	None	I
R/I	0.3262	likely_benign	0.2563	benign	0.48	Stabilizing	0.991	D	0.5	neutral	None	None	None	None	I
R/K	0.1043	likely_benign	0.1002	benign	-0.064	Destabilizing	0.863	D	0.436	neutral	None	None	None	None	I
R/L	0.3006	likely_benign	0.2313	benign	0.48	Stabilizing	0.983	D	0.56	neutral	N	0.477853043	None	None	I
R/M	0.3652	ambiguous	0.2866	benign	-0.01	Destabilizing	0.997	D	0.461	neutral	None	None	None	None	I
R/N	0.6363	likely_pathogenic	0.5228	ambiguous	0.036	Stabilizing	0.939	D	0.419	neutral	None	None	None	None	I
R/P	0.3062	likely_benign	0.2253	benign	0.372	Stabilizing	0.084	N	0.265	neutral	N	0.312187648	None	None	I
R/Q	0.1509	likely_benign	0.1239	benign	0.004	Stabilizing	0.969	D	0.421	neutral	None	None	None	None	I
R/S	0.5552	ambiguous	0.4322	ambiguous	-0.153	Destabilizing	0.533	D	0.22	neutral	N	0.463796662	None	None	I
R/T	0.3337	likely_benign	0.2471	benign	0.018	Stabilizing	0.884	D	0.484	neutral	None	None	None	None	I
R/V	0.3488	ambiguous	0.2833	benign	0.372	Stabilizing	0.969	D	0.501	neutral	None	None	None	None	I
R/W	0.2673	likely_benign	0.2088	benign	-0.362	Destabilizing	0.999	D	0.479	neutral	None	None	None	None	I
R/Y	0.4645	ambiguous	0.3907	ambiguous	0.057	Stabilizing	0.997	D	0.488	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.