TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24872	74839;74840;74841	chr2:178571518;178571517;178571516	chr2:179436245;179436244;179436243
N2AB	23231	69916;69917;69918	chr2:178571518;178571517;178571516	chr2:179436245;179436244;179436243
N2A	22304	67135;67136;67137	chr2:178571518;178571517;178571516	chr2:179436245;179436244;179436243
N2B	15807	47644;47645;47646	chr2:178571518;178571517;178571516	chr2:179436245;179436244;179436243
Novex-1	15932	48019;48020;48021	chr2:178571518;178571517;178571516	chr2:179436245;179436244;179436243
Novex-2	15999	48220;48221;48222	chr2:178571518;178571517;178571516	chr2:179436245;179436244;179436243
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Fn3-68
• Domain position: 65
• Structural Position: 96
• Q(SASA): 0.8442
• 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/K	rs923165795	0.305	0.026	N	0.23	0.129	0.188950314367	gnomAD-2.1.1	7.17E-06	None	None	None	None	I	None	8.27E-05	0	None	0	0	None	0	None	0	0	0
R/K	rs923165795	0.305	0.026	N	0.23	0.129	0.188950314367	gnomAD-3.1.2	1.32E-05	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	4.77555E-04
R/K	rs923165795	0.305	0.026	N	0.23	0.129	0.188950314367	gnomAD-4.0.0	5.1278E-06	None	None	None	None	I	None	5.07666E-05	0	None	0	0	None	0	0	0	0	2.84592E-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	0.7249	likely_pathogenic	0.7383	pathogenic	0.099	Stabilizing	0.919	D	0.496	neutral	None	None	None	None	I
R/C	0.291	likely_benign	0.3045	benign	-0.074	Destabilizing	0.999	D	0.635	neutral	None	None	None	None	I
R/D	0.8569	likely_pathogenic	0.8698	pathogenic	-0.252	Destabilizing	0.976	D	0.486	neutral	None	None	None	None	I
R/E	0.755	likely_pathogenic	0.7677	pathogenic	-0.211	Destabilizing	0.851	D	0.485	neutral	None	None	None	None	I
R/F	0.7853	likely_pathogenic	0.8016	pathogenic	-0.193	Destabilizing	0.988	D	0.611	neutral	None	None	None	None	I
R/G	0.3836	ambiguous	0.4175	ambiguous	-0.046	Destabilizing	0.896	D	0.487	neutral	N	0.398085677	None	None	I
R/H	0.1287	likely_benign	0.1376	benign	-0.573	Destabilizing	0.076	N	0.421	neutral	None	None	None	None	I
R/I	0.7233	likely_pathogenic	0.7519	pathogenic	0.437	Stabilizing	0.984	D	0.595	neutral	N	0.481467188	None	None	I
R/K	0.1665	likely_benign	0.1743	benign	-0.017	Destabilizing	0.026	N	0.23	neutral	N	0.41442614	None	None	I
R/L	0.5284	ambiguous	0.5592	ambiguous	0.437	Stabilizing	0.919	D	0.489	neutral	None	None	None	None	I
R/M	0.621	likely_pathogenic	0.6469	pathogenic	0.006	Stabilizing	0.999	D	0.525	neutral	None	None	None	None	I
R/N	0.6857	likely_pathogenic	0.7144	pathogenic	0.152	Stabilizing	0.919	D	0.498	neutral	None	None	None	None	I
R/P	0.8178	likely_pathogenic	0.849	pathogenic	0.342	Stabilizing	0.988	D	0.545	neutral	None	None	None	None	I
R/Q	0.1976	likely_benign	0.203	benign	0.089	Stabilizing	0.976	D	0.501	neutral	None	None	None	None	I
R/S	0.7307	likely_pathogenic	0.7509	pathogenic	-0.034	Destabilizing	0.896	D	0.507	neutral	N	0.479706983	None	None	I
R/T	0.63	likely_pathogenic	0.6682	pathogenic	0.112	Stabilizing	0.896	D	0.482	neutral	N	0.46893234	None	None	I
R/V	0.7764	likely_pathogenic	0.7935	pathogenic	0.342	Stabilizing	0.988	D	0.575	neutral	None	None	None	None	I
R/W	0.3572	ambiguous	0.3704	ambiguous	-0.367	Destabilizing	0.999	D	0.663	neutral	None	None	None	None	I
R/Y	0.5583	ambiguous	0.5903	pathogenic	0.038	Stabilizing	0.976	D	0.546	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.