TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2307	7144;7145;7146	chr2:178774345;178774344;178774343	chr2:179639072;179639071;179639070
N2AB	2307	7144;7145;7146	chr2:178774345;178774344;178774343	chr2:179639072;179639071;179639070
N2A	2307	7144;7145;7146	chr2:178774345;178774344;178774343	chr2:179639072;179639071;179639070
N2B	2261	7006;7007;7008	chr2:178774345;178774344;178774343	chr2:179639072;179639071;179639070
Novex-1	2261	7006;7007;7008	chr2:178774345;178774344;178774343	chr2:179639072;179639071;179639070
Novex-2	2261	7006;7007;7008	chr2:178774345;178774344;178774343	chr2:179639072;179639071;179639070
Novex-3	2307	7144;7145;7146	chr2:178774345;178774344;178774343	chr2:179639072;179639071;179639070

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-12
• Domain position: 41
• Structural Position: 59
• Q(SASA): 0.5799
• 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
K/T	rs1327919896	0.076	0.001	N	0.148	0.276	0.307016933798	gnomAD-2.1.1	3.18E-05	None	None	None	None	N	None	1.14784E-04	0	None	0	0	None	0	None	0	0	0
K/T	rs1327919896	0.076	0.001	N	0.148	0.276	0.307016933798	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
K/T	rs1327919896	0.076	0.001	N	0.148	0.276	0.307016933798	gnomAD-4.0.0	6.57047E-06	None	None	None	None	N	None	2.41301E-05	0	None	0	0	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
K/A	0.2223	likely_benign	0.2124	benign	0.001	Stabilizing	0.061	N	0.225	neutral	None	None	None	None	N
K/C	0.5267	ambiguous	0.5245	ambiguous	-0.409	Destabilizing	0.983	D	0.259	neutral	None	None	None	None	N
K/D	0.4574	ambiguous	0.4255	ambiguous	0.03	Stabilizing	0.129	N	0.317	neutral	None	None	None	None	N
K/E	0.1515	likely_benign	0.142	benign	0.055	Stabilizing	0.003	N	0.177	neutral	N	0.504011078	None	None	N
K/F	0.5407	ambiguous	0.531	ambiguous	-0.203	Destabilizing	0.716	D	0.324	neutral	None	None	None	None	N
K/G	0.3786	ambiguous	0.3605	ambiguous	-0.193	Destabilizing	0.129	N	0.297	neutral	None	None	None	None	N
K/H	0.1924	likely_benign	0.1881	benign	-0.336	Destabilizing	0.002	N	0.226	neutral	None	None	None	None	N
K/I	0.1993	likely_benign	0.193	benign	0.436	Stabilizing	0.351	N	0.365	neutral	N	0.508824104	None	None	N
K/L	0.2112	likely_benign	0.2055	benign	0.436	Stabilizing	0.129	N	0.325	neutral	None	None	None	None	N
K/M	0.1709	likely_benign	0.1631	benign	0.015	Stabilizing	0.94	D	0.291	neutral	None	None	None	None	N
K/N	0.2471	likely_benign	0.2345	benign	0.013	Stabilizing	0.101	N	0.213	neutral	N	0.501916228	None	None	N
K/P	0.4191	ambiguous	0.416	ambiguous	0.318	Stabilizing	0.593	D	0.339	neutral	None	None	None	None	N
K/Q	0.1009	likely_benign	0.1	benign	-0.07	Destabilizing	0.351	N	0.254	neutral	N	0.503762505	None	None	N
K/R	0.089	likely_benign	0.089	benign	-0.072	Destabilizing	0.183	N	0.249	neutral	N	0.503041927	None	None	N
K/S	0.2491	likely_benign	0.2373	benign	-0.429	Destabilizing	0.001	N	0.138	neutral	None	None	None	None	N
K/T	0.0964	likely_benign	0.0914	benign	-0.252	Destabilizing	0.001	N	0.148	neutral	N	0.508867805	None	None	N
K/V	0.1985	likely_benign	0.1927	benign	0.318	Stabilizing	0.129	N	0.35	neutral	None	None	None	None	N
K/W	0.6761	likely_pathogenic	0.6737	pathogenic	-0.276	Destabilizing	0.983	D	0.263	neutral	None	None	None	None	N
K/Y	0.4583	ambiguous	0.45	ambiguous	0.086	Stabilizing	0.557	D	0.341	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.