TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28294	85105;85106;85107	chr2:178561252;178561251;178561250	chr2:179425979;179425978;179425977
N2AB	26653	80182;80183;80184	chr2:178561252;178561251;178561250	chr2:179425979;179425978;179425977
N2A	25726	77401;77402;77403	chr2:178561252;178561251;178561250	chr2:179425979;179425978;179425977
N2B	19229	57910;57911;57912	chr2:178561252;178561251;178561250	chr2:179425979;179425978;179425977
Novex-1	19354	58285;58286;58287	chr2:178561252;178561251;178561250	chr2:179425979;179425978;179425977
Novex-2	19421	58486;58487;58488	chr2:178561252;178561251;178561250	chr2:179425979;179425978;179425977
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Fn3-94
• Domain position: 43
• Structural Position: 50
• Q(SASA): 0.3862
• 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
L/V	rs747855990	-1.461	0.999	N	0.561	0.152	0.471941563831	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
L/V	rs747855990	-1.461	0.999	N	0.561	0.152	0.471941563831	gnomAD-4.0.0	1.59139E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85811E-06	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
L/A	0.6567	likely_pathogenic	0.6406	pathogenic	-2.297	Highly Destabilizing	0.999	D	0.626	neutral	None	None	None	None	N
L/C	0.762	likely_pathogenic	0.767	pathogenic	-1.304	Destabilizing	1.0	D	0.613	neutral	None	None	None	None	N
L/D	0.93	likely_pathogenic	0.919	pathogenic	-2.233	Highly Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
L/E	0.792	likely_pathogenic	0.7708	pathogenic	-2.141	Highly Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
L/F	0.3741	ambiguous	0.3497	ambiguous	-1.444	Destabilizing	1.0	D	0.663	neutral	None	None	None	None	N
L/G	0.8172	likely_pathogenic	0.8122	pathogenic	-2.704	Highly Destabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	N
L/H	0.6238	likely_pathogenic	0.6079	pathogenic	-1.971	Destabilizing	1.0	D	0.678	prob.neutral	None	None	None	None	N
L/I	0.1493	likely_benign	0.1271	benign	-1.177	Destabilizing	0.999	D	0.512	neutral	N	0.50280006	None	None	N
L/K	0.7231	likely_pathogenic	0.7204	pathogenic	-1.615	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
L/M	0.1861	likely_benign	0.1853	benign	-0.93	Destabilizing	1.0	D	0.63	neutral	None	None	None	None	N
L/N	0.7262	likely_pathogenic	0.6985	pathogenic	-1.56	Destabilizing	1.0	D	0.704	prob.neutral	None	None	None	None	N
L/P	0.9024	likely_pathogenic	0.8857	pathogenic	-1.527	Destabilizing	1.0	D	0.703	prob.neutral	N	0.511592902	None	None	N
L/Q	0.5093	ambiguous	0.5076	ambiguous	-1.661	Destabilizing	1.0	D	0.709	prob.delet.	N	0.478508355	None	None	N
L/R	0.6725	likely_pathogenic	0.677	pathogenic	-1.063	Destabilizing	1.0	D	0.731	prob.delet.	D	0.52407941	None	None	N
L/S	0.7428	likely_pathogenic	0.7272	pathogenic	-2.187	Highly Destabilizing	1.0	D	0.72	prob.delet.	None	None	None	None	N
L/T	0.6241	likely_pathogenic	0.603	pathogenic	-1.987	Destabilizing	1.0	D	0.71	prob.delet.	None	None	None	None	N
L/V	0.2028	likely_benign	0.1856	benign	-1.527	Destabilizing	0.999	D	0.561	neutral	N	0.465684467	None	None	N
L/W	0.5798	likely_pathogenic	0.5728	pathogenic	-1.668	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
L/Y	0.6157	likely_pathogenic	0.5853	pathogenic	-1.455	Destabilizing	1.0	D	0.675	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.