TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15865	47818;47819;47820	chr2:178617492;178617491;178617490	chr2:179482219;179482218;179482217
N2AB	14224	42895;42896;42897	chr2:178617492;178617491;178617490	chr2:179482219;179482218;179482217
N2A	13297	40114;40115;40116	chr2:178617492;178617491;178617490	chr2:179482219;179482218;179482217
N2B	6800	20623;20624;20625	chr2:178617492;178617491;178617490	chr2:179482219;179482218;179482217
Novex-1	6925	20998;20999;21000	chr2:178617492;178617491;178617490	chr2:179482219;179482218;179482217
Novex-2	6992	21199;21200;21201	chr2:178617492;178617491;178617490	chr2:179482219;179482218;179482217
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Fn3-3
• Domain position: 7
• Structural Position: 7
• Q(SASA): 0.4015
• 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
N/S	rs2057560011	None	0.994	N	0.451	0.288	0.243398259712	gnomAD-3.1.2	1.32E-05	None	None	None	None	I	None	0	0	0	0	0	None	1.88253E-04	0	0	0	0
N/S	rs2057560011	None	0.994	N	0.451	0.288	0.243398259712	gnomAD-4.0.0	1.31725E-05	None	None	None	None	I	None	0	0	None	0	0	None	1.88253E-04	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
N/A	0.3032	likely_benign	0.3487	ambiguous	-0.209	Destabilizing	0.992	D	0.563	neutral	None	None	None	None	I
N/C	0.3445	ambiguous	0.3842	ambiguous	0.256	Stabilizing	0.46	N	0.443	neutral	None	None	None	None	I
N/D	0.1994	likely_benign	0.2469	benign	0.124	Stabilizing	0.998	D	0.517	neutral	N	0.489198181	None	None	I
N/E	0.4744	ambiguous	0.5424	ambiguous	0.088	Stabilizing	1.0	D	0.585	neutral	None	None	None	None	I
N/F	0.5102	ambiguous	0.5804	pathogenic	-0.591	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	I
N/G	0.3234	likely_benign	0.375	ambiguous	-0.375	Destabilizing	0.996	D	0.461	neutral	None	None	None	None	I
N/H	0.1445	likely_benign	0.1522	benign	-0.381	Destabilizing	0.999	D	0.595	neutral	D	0.539495373	None	None	I
N/I	0.3375	likely_benign	0.4123	ambiguous	0.137	Stabilizing	0.998	D	0.756	deleterious	D	0.569314579	None	None	I
N/K	0.3459	ambiguous	0.4039	ambiguous	0.072	Stabilizing	0.999	D	0.59	neutral	N	0.491959431	None	None	I
N/L	0.3107	likely_benign	0.3595	ambiguous	0.137	Stabilizing	0.998	D	0.649	neutral	None	None	None	None	I
N/M	0.4256	ambiguous	0.4892	ambiguous	0.306	Stabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	I
N/P	0.8129	likely_pathogenic	0.86	pathogenic	0.048	Stabilizing	1.0	D	0.751	deleterious	None	None	None	None	I
N/Q	0.3952	ambiguous	0.4241	ambiguous	-0.381	Destabilizing	1.0	D	0.613	neutral	None	None	None	None	I
N/R	0.3823	ambiguous	0.3979	ambiguous	0.113	Stabilizing	1.0	D	0.614	neutral	None	None	None	None	I
N/S	0.1189	likely_benign	0.1304	benign	-0.154	Destabilizing	0.994	D	0.451	neutral	N	0.489965576	None	None	I
N/T	0.2166	likely_benign	0.2505	benign	-0.052	Destabilizing	0.994	D	0.552	neutral	N	0.521680427	None	None	I
N/V	0.3669	ambiguous	0.4247	ambiguous	0.048	Stabilizing	0.998	D	0.726	prob.delet.	None	None	None	None	I
N/W	0.8101	likely_pathogenic	0.8332	pathogenic	-0.617	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	I
N/Y	0.1962	likely_benign	0.2199	benign	-0.334	Destabilizing	0.999	D	0.753	deleterious	D	0.694911738	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.