TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22058	66397;66398;66399	chr2:178582197;178582196;178582195	chr2:179446924;179446923;179446922
N2AB	20417	61474;61475;61476	chr2:178582197;178582196;178582195	chr2:179446924;179446923;179446922
N2A	19490	58693;58694;58695	chr2:178582197;178582196;178582195	chr2:179446924;179446923;179446922
N2B	12993	39202;39203;39204	chr2:178582197;178582196;178582195	chr2:179446924;179446923;179446922
Novex-1	13118	39577;39578;39579	chr2:178582197;178582196;178582195	chr2:179446924;179446923;179446922
Novex-2	13185	39778;39779;39780	chr2:178582197;178582196;178582195	chr2:179446924;179446923;179446922
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: Fn3-48
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.5666
• 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	rs199643269	-0.454	0.997	N	0.341	0.284	None	gnomAD-2.1.1	1.113E-04	None	None	None	None	N	None	7.96579E-04	6.08E-05	None	0	0	None	7.17E-05	None	0	4.82E-05	1.44844E-04
R/C	rs199643269	-0.454	0.997	N	0.341	0.284	None	gnomAD-3.1.2	3.88224E-04	None	None	None	None	N	None	1.30365E-03	6.57E-05	0	0	0	None	0	0	4.41E-05	0	4.78927E-04
R/C	rs199643269	-0.454	0.997	N	0.341	0.284	None	1000 genomes	1.99681E-04	None	None	None	None	N	None	8E-04	0	None	None	0	0	None	None	None	0	None
R/C	rs199643269	-0.454	0.997	N	0.341	0.284	None	gnomAD-4.0.0	8.41867E-05	None	None	None	None	N	None	1.18784E-03	8.75289E-05	None	0	0	None	0	0	2.63325E-05	5.65713E-05	9.66713E-05
R/H	rs753077711	-1.206	0.971	N	0.381	0.206	0.306053231325	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
R/H	rs753077711	-1.206	0.971	N	0.381	0.206	0.306053231325	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
R/H	rs753077711	-1.206	0.971	N	0.381	0.206	0.306053231325	gnomAD-4.0.0	3.73232E-06	None	None	None	None	N	None	0	0	None	0	2.23774E-05	None	0	0	1.69746E-06	3.35751E-05	0
R/L	rs753077711	0.055	0.465	N	0.325	0.168	0.371157983038	gnomAD-2.1.1	4.13E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.09E-06	0
R/L	rs753077711	0.055	0.465	N	0.325	0.168	0.371157983038	gnomAD-4.0.0	2.06103E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.70212E-06	0	0
R/S	None	None	0.465	N	0.244	0.235	0.268660756437	gnomAD-4.0.0	1.3779E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.80296E-06	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	0.2318	likely_benign	0.2043	benign	-0.062	Destabilizing	0.165	N	0.215	neutral	None	None	None	None	N
R/C	0.1381	likely_benign	0.1132	benign	-0.041	Destabilizing	0.997	D	0.341	neutral	N	0.48819318	None	None	N
R/D	0.6469	likely_pathogenic	0.5886	pathogenic	-0.033	Destabilizing	0.312	N	0.381	neutral	None	None	None	None	N
R/E	0.3423	ambiguous	0.3088	benign	0.016	Stabilizing	0.185	N	0.155	neutral	None	None	None	None	N
R/F	0.5282	ambiguous	0.4676	ambiguous	-0.328	Destabilizing	0.96	D	0.44	neutral	None	None	None	None	N
R/G	0.248	likely_benign	0.2025	benign	-0.242	Destabilizing	0.465	N	0.313	neutral	N	0.477072109	None	None	N
R/H	0.1249	likely_benign	0.1114	benign	-0.749	Destabilizing	0.971	D	0.381	neutral	N	0.506778941	None	None	N
R/I	0.223	likely_benign	0.2039	benign	0.375	Stabilizing	0.887	D	0.514	neutral	None	None	None	None	N
R/K	0.0969	likely_benign	0.0993	benign	-0.009	Destabilizing	0.001	N	0.091	neutral	None	None	None	None	N
R/L	0.227	likely_benign	0.2082	benign	0.375	Stabilizing	0.465	N	0.325	neutral	N	0.468393911	None	None	N
R/M	0.2577	likely_benign	0.2355	benign	0.094	Stabilizing	0.96	D	0.424	neutral	None	None	None	None	N
R/N	0.4785	ambiguous	0.4463	ambiguous	0.356	Stabilizing	0.524	D	0.284	neutral	None	None	None	None	N
R/P	0.1359	likely_benign	0.1291	benign	0.249	Stabilizing	0.001	N	0.074	neutral	N	0.359068716	None	None	N
R/Q	0.0964	likely_benign	0.0895	benign	0.178	Stabilizing	0.018	N	0.13	neutral	None	None	None	None	N
R/S	0.3595	ambiguous	0.3149	benign	-0.047	Destabilizing	0.465	N	0.244	neutral	N	0.437687002	None	None	N
R/T	0.2307	likely_benign	0.2055	benign	0.127	Stabilizing	0.312	N	0.289	neutral	None	None	None	None	N
R/V	0.2807	likely_benign	0.2563	benign	0.249	Stabilizing	0.691	D	0.507	neutral	None	None	None	None	N
R/W	0.3011	likely_benign	0.2547	benign	-0.358	Destabilizing	0.989	D	0.338	neutral	None	None	None	None	N
R/Y	0.4028	ambiguous	0.3508	ambiguous	0.049	Stabilizing	0.96	D	0.507	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.