TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27737	83434;83435;83436	chr2:178562923;178562922;178562921	chr2:179427650;179427649;179427648
N2AB	26096	78511;78512;78513	chr2:178562923;178562922;178562921	chr2:179427650;179427649;179427648
N2A	25169	75730;75731;75732	chr2:178562923;178562922;178562921	chr2:179427650;179427649;179427648
N2B	18672	56239;56240;56241	chr2:178562923;178562922;178562921	chr2:179427650;179427649;179427648
Novex-1	18797	56614;56615;56616	chr2:178562923;178562922;178562921	chr2:179427650;179427649;179427648
Novex-2	18864	56815;56816;56817	chr2:178562923;178562922;178562921	chr2:179427650;179427649;179427648
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-141
• Domain position: 62
• Structural Position: 145
• Q(SASA): 0.2973
• Predicted PPI site: I

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
T/A	rs764871079	-0.783	0.166	N	0.254	0.16	0.240491677333	gnomAD-2.1.1	1.61E-05	None	None	None	None	I	None	0	0	None	0	1.68161E-04	None	0	None	0	0	1.66058E-04
T/A	rs764871079	-0.783	0.166	N	0.254	0.16	0.240491677333	gnomAD-4.0.0	7.95874E-06	None	None	None	None	I	None	0	0	None	0	1.11235E-04	None	0	0	0	1.43275E-05	0
T/N	None	None	None	N	0.136	0.125	0.238705975628	gnomAD-4.0.0	1.59178E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85876E-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
T/A	0.154	likely_benign	0.1623	benign	-1.186	Destabilizing	0.166	N	0.254	neutral	N	0.512817558	None	None	I
T/C	0.4708	ambiguous	0.4682	ambiguous	-0.797	Destabilizing	0.991	D	0.423	neutral	None	None	None	None	I
T/D	0.259	likely_benign	0.2415	benign	-0.559	Destabilizing	0.001	N	0.147	neutral	None	None	None	None	I
T/E	0.4819	ambiguous	0.5048	ambiguous	-0.529	Destabilizing	0.209	N	0.429	neutral	None	None	None	None	I
T/F	0.5633	ambiguous	0.5728	pathogenic	-1.291	Destabilizing	0.901	D	0.439	neutral	None	None	None	None	I
T/G	0.2039	likely_benign	0.199	benign	-1.453	Destabilizing	0.209	N	0.361	neutral	None	None	None	None	I
T/H	0.3126	likely_benign	0.3078	benign	-1.71	Destabilizing	0.901	D	0.437	neutral	None	None	None	None	I
T/I	0.5679	likely_pathogenic	0.5745	pathogenic	-0.548	Destabilizing	0.662	D	0.494	neutral	N	0.486239442	None	None	I
T/K	0.3938	ambiguous	0.4214	ambiguous	-0.783	Destabilizing	0.345	N	0.421	neutral	None	None	None	None	I
T/L	0.1914	likely_benign	0.1977	benign	-0.548	Destabilizing	0.561	D	0.412	neutral	None	None	None	None	I
T/M	0.167	likely_benign	0.173	benign	-0.166	Destabilizing	0.965	D	0.433	neutral	None	None	None	None	I
T/N	0.0602	likely_benign	0.0531	benign	-0.848	Destabilizing	None	N	0.136	neutral	N	0.414770936	None	None	I
T/P	0.5041	ambiguous	0.5097	ambiguous	-0.731	Destabilizing	0.662	D	0.474	neutral	N	0.509205542	None	None	I
T/Q	0.3304	likely_benign	0.3448	ambiguous	-1.034	Destabilizing	0.561	D	0.473	neutral	None	None	None	None	I
T/R	0.3804	ambiguous	0.4126	ambiguous	-0.57	Destabilizing	0.561	D	0.435	neutral	None	None	None	None	I
T/S	0.0783	likely_benign	0.0733	benign	-1.178	Destabilizing	0.005	N	0.173	neutral	N	0.477627549	None	None	I
T/V	0.3982	ambiguous	0.4034	ambiguous	-0.731	Destabilizing	0.561	D	0.227	neutral	None	None	None	None	I
T/W	0.8382	likely_pathogenic	0.842	pathogenic	-1.177	Destabilizing	0.991	D	0.451	neutral	None	None	None	None	I
T/Y	0.4953	ambiguous	0.4936	ambiguous	-0.936	Destabilizing	0.965	D	0.437	neutral	None	None	None	None	I

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.