TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24013	72262;72263;72264	chr2:178574095;178574094;178574093	chr2:179438822;179438821;179438820
N2AB	22372	67339;67340;67341	chr2:178574095;178574094;178574093	chr2:179438822;179438821;179438820
N2A	21445	64558;64559;64560	chr2:178574095;178574094;178574093	chr2:179438822;179438821;179438820
N2B	14948	45067;45068;45069	chr2:178574095;178574094;178574093	chr2:179438822;179438821;179438820
Novex-1	15073	45442;45443;45444	chr2:178574095;178574094;178574093	chr2:179438822;179438821;179438820
Novex-2	15140	45643;45644;45645	chr2:178574095;178574094;178574093	chr2:179438822;179438821;179438820
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: Fn3-62
• Domain position: 90
• Structural Position: 122
• Q(SASA): 0.7185
• 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/D	rs529670209	-0.399	0.006	N	0.163	0.044	0.144782658237	gnomAD-2.1.1	3.93E-05	None	None	None	None	N	None	0	3.11192E-04	None	0	0	None	0	None	0	0	0
E/D	rs529670209	-0.399	0.006	N	0.163	0.044	0.144782658237	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	0	1.96541E-04	0	0	0	None	0	0	0	0	0
E/D	rs529670209	-0.399	0.006	N	0.163	0.044	0.144782658237	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	1.4E-03	None	None	0	0	None	None	None	0	None
E/D	rs529670209	-0.399	0.006	N	0.163	0.044	0.144782658237	gnomAD-4.0.0	9.91653E-06	None	None	None	None	N	None	1.3334E-05	1.83333E-04	None	0	0	None	0	0	8.47772E-07	0	4.80184E-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
E/A	0.131	likely_benign	0.1436	benign	-0.424	Destabilizing	0.651	D	0.373	neutral	N	0.452578242	None	None	N
E/C	0.8197	likely_pathogenic	0.8443	pathogenic	-0.203	Destabilizing	0.995	D	0.585	neutral	None	None	None	None	N
E/D	0.1272	likely_benign	0.1356	benign	-0.393	Destabilizing	0.006	N	0.163	neutral	N	0.479912053	None	None	N
E/F	0.6286	likely_pathogenic	0.6655	pathogenic	-0.171	Destabilizing	0.982	D	0.526	neutral	None	None	None	None	N
E/G	0.166	likely_benign	0.1815	benign	-0.636	Destabilizing	0.651	D	0.382	neutral	N	0.476722885	None	None	N
E/H	0.445	ambiguous	0.4803	ambiguous	0.137	Stabilizing	0.946	D	0.334	neutral	None	None	None	None	N
E/I	0.2338	likely_benign	0.2501	benign	0.108	Stabilizing	0.946	D	0.562	neutral	None	None	None	None	N
E/K	0.1128	likely_benign	0.1273	benign	0.218	Stabilizing	0.024	N	0.177	neutral	N	0.502135552	None	None	N
E/L	0.257	likely_benign	0.2919	benign	0.108	Stabilizing	0.712	D	0.509	neutral	None	None	None	None	N
E/M	0.3228	likely_benign	0.3552	ambiguous	0.133	Stabilizing	0.995	D	0.47	neutral	None	None	None	None	N
E/N	0.2487	likely_benign	0.2737	benign	-0.2	Destabilizing	0.553	D	0.373	neutral	None	None	None	None	N
E/P	0.4009	ambiguous	0.382	ambiguous	-0.049	Destabilizing	0.946	D	0.43	neutral	None	None	None	None	N
E/Q	0.1233	likely_benign	0.1321	benign	-0.142	Destabilizing	0.068	N	0.16	neutral	N	0.456060962	None	None	N
E/R	0.2341	likely_benign	0.2547	benign	0.51	Stabilizing	0.553	D	0.335	neutral	None	None	None	None	N
E/S	0.1942	likely_benign	0.2106	benign	-0.356	Destabilizing	0.712	D	0.3	neutral	None	None	None	None	N
E/T	0.2081	likely_benign	0.2278	benign	-0.177	Destabilizing	0.834	D	0.402	neutral	None	None	None	None	N
E/V	0.1499	likely_benign	0.161	benign	-0.049	Destabilizing	0.93	D	0.468	neutral	N	0.473786824	None	None	N
E/W	0.8773	likely_pathogenic	0.8943	pathogenic	0.02	Stabilizing	0.995	D	0.629	neutral	None	None	None	None	N
E/Y	0.504	ambiguous	0.5456	ambiguous	0.078	Stabilizing	0.982	D	0.495	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.