TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1890	5893;5894;5895	chr2:178776196;178776195;178776194	chr2:179640923;179640922;179640921
N2AB	1890	5893;5894;5895	chr2:178776196;178776195;178776194	chr2:179640923;179640922;179640921
N2A	1890	5893;5894;5895	chr2:178776196;178776195;178776194	chr2:179640923;179640922;179640921
N2B	1844	5755;5756;5757	chr2:178776196;178776195;178776194	chr2:179640923;179640922;179640921
Novex-1	1844	5755;5756;5757	chr2:178776196;178776195;178776194	chr2:179640923;179640922;179640921
Novex-2	1844	5755;5756;5757	chr2:178776196;178776195;178776194	chr2:179640923;179640922;179640921
Novex-3	1890	5893;5894;5895	chr2:178776196;178776195;178776194	chr2:179640923;179640922;179640921

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGC
• RefSeq wild type template codon: GCG
• Domain: Ig-9
• Domain position: 50
• Structural Position: 125
• Q(SASA): 0.443
• 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	rs146496197	-0.491	1.0	D	0.487	0.626	None	gnomAD-2.1.1	4.07244E-04	None	None	None	None	N	None	2.68408E-03	4.51671E-04	None	0	0	None	3.27E-05	None	0	2.17466E-04	4.15858E-04
R/C	rs146496197	-0.491	1.0	D	0.487	0.626	None	gnomAD-3.1.2	1.03209E-03	None	None	None	None	N	None	2.96901E-03	9.1683E-04	0	0	0	None	0	3.16456E-03	2.35211E-04	2.07469E-04	9.56938E-04
R/C	rs146496197	-0.491	1.0	D	0.487	0.626	None	1000 genomes	5.99042E-04	None	None	None	None	N	None	1.5E-03	1.4E-03	None	None	0	0	None	None	None	0	None
R/C	rs146496197	-0.491	1.0	D	0.487	0.626	None	gnomAD-4.0.0	3.25884E-04	None	None	None	None	N	None	2.66581E-03	6.33186E-04	None	0	0	None	3.12451E-05	8.2481E-04	2.09325E-04	4.39213E-05	4.79954E-04
R/H	rs370027329	-1.61	0.169	N	0.137	0.365	None	gnomAD-2.1.1	1.06E-05	None	None	None	None	N	None	4.01E-05	2.82E-05	None	0	0	None	0	None	0	7.77E-06	0
R/H	rs370027329	-1.61	0.169	N	0.137	0.365	None	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	2.41E-05	6.55E-05	0	0	0	None	0	0	0	0	0
R/H	rs370027329	-1.61	0.169	N	0.137	0.365	None	gnomAD-4.0.0	7.43487E-06	None	None	None	None	N	None	1.33483E-05	1.66683E-05	None	0	4.45434E-05	None	0	0	5.93216E-06	0	1.60036E-05
R/P	rs370027329	-0.392	0.998	N	0.467	0.493	0.497871611283	gnomAD-2.1.1	3.98E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.82E-06	0
R/P	rs370027329	-0.392	0.998	N	0.467	0.493	0.497871611283	gnomAD-4.0.0	6.84068E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99302E-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	0.8868	likely_pathogenic	0.8718	pathogenic	-0.757	Destabilizing	0.939	D	0.397	neutral	None	None	None	None	N
R/C	0.6679	likely_pathogenic	0.6141	pathogenic	-0.625	Destabilizing	1.0	D	0.487	neutral	D	0.554837651	None	None	N
R/D	0.9581	likely_pathogenic	0.953	pathogenic	0.031	Stabilizing	0.884	D	0.447	neutral	None	None	None	None	N
R/E	0.8795	likely_pathogenic	0.8546	pathogenic	0.191	Stabilizing	0.759	D	0.367	neutral	None	None	None	None	N
R/F	0.9077	likely_pathogenic	0.8901	pathogenic	-0.337	Destabilizing	0.991	D	0.482	neutral	None	None	None	None	N
R/G	0.7985	likely_pathogenic	0.7807	pathogenic	-1.111	Destabilizing	0.967	D	0.434	neutral	N	0.465582382	None	None	N
R/H	0.3186	likely_benign	0.265	benign	-1.406	Destabilizing	0.169	N	0.137	neutral	N	0.446157856	None	None	N
R/I	0.7883	likely_pathogenic	0.7428	pathogenic	0.211	Stabilizing	0.997	D	0.487	neutral	None	None	None	None	N
R/K	0.338	likely_benign	0.3048	benign	-0.688	Destabilizing	0.759	D	0.394	neutral	None	None	None	None	N
R/L	0.7134	likely_pathogenic	0.6682	pathogenic	0.211	Stabilizing	0.983	D	0.438	neutral	N	0.438780731	None	None	N
R/M	0.8563	likely_pathogenic	0.82	pathogenic	-0.236	Destabilizing	0.999	D	0.413	neutral	None	None	None	None	N
R/N	0.9095	likely_pathogenic	0.8943	pathogenic	-0.246	Destabilizing	0.17	N	0.209	neutral	None	None	None	None	N
R/P	0.9814	likely_pathogenic	0.9837	pathogenic	-0.091	Destabilizing	0.998	D	0.467	neutral	N	0.503306533	None	None	N
R/Q	0.3811	ambiguous	0.3249	benign	-0.297	Destabilizing	0.579	D	0.203	neutral	None	None	None	None	N
R/S	0.886	likely_pathogenic	0.8673	pathogenic	-0.994	Destabilizing	0.967	D	0.399	neutral	N	0.444515909	None	None	N
R/T	0.8099	likely_pathogenic	0.7711	pathogenic	-0.633	Destabilizing	0.939	D	0.404	neutral	None	None	None	None	N
R/V	0.8305	likely_pathogenic	0.7988	pathogenic	-0.091	Destabilizing	0.991	D	0.455	neutral	None	None	None	None	N
R/W	0.6265	likely_pathogenic	0.5689	pathogenic	0.032	Stabilizing	0.999	D	0.555	neutral	None	None	None	None	N
R/Y	0.8106	likely_pathogenic	0.7833	pathogenic	0.285	Stabilizing	0.982	D	0.461	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.