TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27520	82783;82784;82785	chr2:178563574;178563573;178563572	chr2:179428301;179428300;179428299
N2AB	25879	77860;77861;77862	chr2:178563574;178563573;178563572	chr2:179428301;179428300;179428299
N2A	24952	75079;75080;75081	chr2:178563574;178563573;178563572	chr2:179428301;179428300;179428299
N2B	18455	55588;55589;55590	chr2:178563574;178563573;178563572	chr2:179428301;179428300;179428299
Novex-1	18580	55963;55964;55965	chr2:178563574;178563573;178563572	chr2:179428301;179428300;179428299
Novex-2	18647	56164;56165;56166	chr2:178563574;178563573;178563572	chr2:179428301;179428300;179428299
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Fn3-88
• Domain position: 52
• Structural Position: 69
• Q(SASA): 0.1893
• 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
N/D	None	None	0.999	N	0.603	0.464	0.439445477881	gnomAD-4.0.0	1.36842E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.15931E-05	1.65656E-05
N/K	rs56264840	-0.273	1.0	N	0.714	0.423	0.250039746154	gnomAD-2.1.1	3.30797E-03	None	None	None	None	N	None	1.23967E-04	8.19858E-04	None	1.0628E-03	0	None	2.0979E-02	None	4E-05	1.71805E-03	2.94283E-03
N/K	rs56264840	-0.273	1.0	N	0.714	0.423	0.250039746154	gnomAD-3.1.2	1.72212E-03	None	None	None	None	N	None	1.68952E-04	1.7038E-03	0	8.64553E-04	0	None	0	0	1.67593E-03	2.25673E-02	1.43267E-03
N/K	rs56264840	-0.273	1.0	N	0.714	0.423	0.250039746154	1000 genomes	5.79073E-03	None	None	None	None	N	None	0	1.4E-03	None	None	0	2E-03	None	None	None	2.66E-02	None
N/K	rs56264840	-0.273	1.0	N	0.714	0.423	0.250039746154	gnomAD-4.0.0	2.11365E-03	None	None	None	None	N	None	2.39955E-04	9.83301E-04	None	8.44595E-04	4.45911E-05	None	6.24766E-05	4.12541E-03	1.06462E-03	2.03878E-02	2.64068E-03
N/S	None	None	0.999	N	0.567	0.253	0.278143212241	gnomAD-4.0.0	2.05263E-06	None	None	None	None	N	None	0	0	None	0	2.51978E-05	None	0	0	0	0	3.31312E-05
N/T	None	None	0.999	N	0.677	0.246	0.315903272564	gnomAD-4.0.0	6.84209E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.65656E-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
N/A	0.4883	ambiguous	0.4955	ambiguous	-0.883	Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	N
N/C	0.3161	likely_benign	0.3112	benign	-0.027	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
N/D	0.5572	ambiguous	0.5325	ambiguous	-0.383	Destabilizing	0.999	D	0.603	neutral	N	0.488525215	None	None	N
N/E	0.8803	likely_pathogenic	0.8857	pathogenic	-0.267	Destabilizing	0.999	D	0.691	prob.neutral	None	None	None	None	N
N/F	0.8222	likely_pathogenic	0.8086	pathogenic	-0.583	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
N/G	0.4107	ambiguous	0.406	ambiguous	-1.24	Destabilizing	0.999	D	0.561	neutral	None	None	None	None	N
N/H	0.191	likely_benign	0.1871	benign	-0.919	Destabilizing	1.0	D	0.755	deleterious	N	0.520599174	None	None	N
N/I	0.506	ambiguous	0.5167	ambiguous	0.034	Stabilizing	1.0	D	0.792	deleterious	N	0.483512012	None	None	N
N/K	0.8527	likely_pathogenic	0.8649	pathogenic	-0.223	Destabilizing	1.0	D	0.714	prob.delet.	N	0.492715497	None	None	N
N/L	0.4265	ambiguous	0.4511	ambiguous	0.034	Stabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
N/M	0.5921	likely_pathogenic	0.5971	pathogenic	0.398	Stabilizing	1.0	D	0.752	deleterious	None	None	None	None	N
N/P	0.8223	likely_pathogenic	0.8545	pathogenic	-0.241	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
N/Q	0.6861	likely_pathogenic	0.6959	pathogenic	-0.777	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
N/R	0.7921	likely_pathogenic	0.8129	pathogenic	-0.316	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	N
N/S	0.0809	likely_benign	0.0849	benign	-0.908	Destabilizing	0.999	D	0.567	neutral	N	0.499413038	None	None	N
N/T	0.1701	likely_benign	0.1753	benign	-0.587	Destabilizing	0.999	D	0.677	prob.neutral	N	0.492967069	None	None	N
N/V	0.4504	ambiguous	0.4545	ambiguous	-0.241	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
N/W	0.9142	likely_pathogenic	0.9157	pathogenic	-0.331	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	N
N/Y	0.4693	ambiguous	0.4603	ambiguous	-0.124	Destabilizing	1.0	D	0.777	deleterious	D	0.523812838	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.