TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18038	54337;54338;54339	chr2:178605065;178605064;178605063	chr2:179469792;179469791;179469790
N2AB	16397	49414;49415;49416	chr2:178605065;178605064;178605063	chr2:179469792;179469791;179469790
N2A	15470	46633;46634;46635	chr2:178605065;178605064;178605063	chr2:179469792;179469791;179469790
N2B	8973	27142;27143;27144	chr2:178605065;178605064;178605063	chr2:179469792;179469791;179469790
Novex-1	9098	27517;27518;27519	chr2:178605065;178605064;178605063	chr2:179469792;179469791;179469790
Novex-2	9165	27718;27719;27720	chr2:178605065;178605064;178605063	chr2:179469792;179469791;179469790
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-114
• Domain position: 71
• Structural Position: 148
• Q(SASA): 0.5167
• 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
E/K	rs527887963	None	0.012	N	0.127	0.024	0.0920862733494	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	1.09649E-03	0	0	None	0	0	0	0	0
E/K	rs527887963	None	0.012	N	0.127	0.024	0.0920862733494	gnomAD-4.0.0	6.58137E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	0
E/Q	rs527887963	0.219	0.001	N	0.167	0.026	0.0611884634855	gnomAD-2.1.1	1.62E-05	None	None	None	None	N	None	0	0	None	0	2.23789E-04	None	0	None	0	0	0
E/Q	rs527887963	0.219	0.001	N	0.167	0.026	0.0611884634855	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	1.9478E-04	None	0	0	0	0	0
E/Q	rs527887963	0.219	0.001	N	0.167	0.026	0.0611884634855	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	0	None	None	1E-03	0	None	None	None	0	None
E/Q	rs527887963	0.219	0.001	N	0.167	0.026	0.0611884634855	gnomAD-4.0.0	1.02648E-05	None	None	None	None	N	None	0	0	None	0	1.94647E-04	None	0	0	0	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
E/A	0.0776	likely_benign	0.1068	benign	-0.265	Destabilizing	None	N	0.072	neutral	N	0.465734821	None	None	N
E/C	0.6635	likely_pathogenic	0.74	pathogenic	-0.175	Destabilizing	0.356	N	0.195	neutral	None	None	None	None	N
E/D	0.0918	likely_benign	0.0967	benign	-0.343	Destabilizing	None	N	0.088	neutral	N	0.441876527	None	None	N
E/F	0.6089	likely_pathogenic	0.7074	pathogenic	-0.102	Destabilizing	0.214	N	0.288	neutral	None	None	None	None	N
E/G	0.0942	likely_benign	0.1112	benign	-0.448	Destabilizing	None	N	0.07	neutral	N	0.477933327	None	None	N
E/H	0.3083	likely_benign	0.381	ambiguous	0.328	Stabilizing	0.356	N	0.169	neutral	None	None	None	None	N
E/I	0.249	likely_benign	0.3286	benign	0.18	Stabilizing	0.038	N	0.335	neutral	None	None	None	None	N
E/K	0.1227	likely_benign	0.1357	benign	0.351	Stabilizing	0.012	N	0.127	neutral	N	0.457192696	None	None	N
E/L	0.2446	likely_benign	0.348	ambiguous	0.18	Stabilizing	None	N	0.135	neutral	None	None	None	None	N
E/M	0.3029	likely_benign	0.3941	ambiguous	0.103	Stabilizing	0.214	N	0.205	neutral	None	None	None	None	N
E/N	0.1281	likely_benign	0.1645	benign	-0.053	Destabilizing	0.016	N	0.11	neutral	None	None	None	None	N
E/P	0.4531	ambiguous	0.5697	pathogenic	0.051	Stabilizing	0.136	N	0.267	neutral	None	None	None	None	N
E/Q	0.1065	likely_benign	0.1299	benign	-0.005	Destabilizing	0.001	N	0.167	neutral	N	0.427909939	None	None	N
E/R	0.2153	likely_benign	0.2446	benign	0.632	Stabilizing	None	N	0.077	neutral	None	None	None	None	N
E/S	0.0989	likely_benign	0.1317	benign	-0.19	Destabilizing	None	N	0.093	neutral	None	None	None	None	N
E/T	0.1108	likely_benign	0.1516	benign	-0.033	Destabilizing	0.016	N	0.187	neutral	None	None	None	None	N
E/V	0.1539	likely_benign	0.1998	benign	0.051	Stabilizing	0.012	N	0.17	neutral	N	0.490190548	None	None	N
E/W	0.7797	likely_pathogenic	0.8272	pathogenic	0.041	Stabilizing	0.864	D	0.201	neutral	None	None	None	None	N
E/Y	0.4842	ambiguous	0.57	pathogenic	0.141	Stabilizing	0.356	N	0.273	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.