TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18403	55432;55433;55434	chr2:178602064;178602063;178602062	chr2:179466791;179466790;179466789
N2AB	16762	50509;50510;50511	chr2:178602064;178602063;178602062	chr2:179466791;179466790;179466789
N2A	15835	47728;47729;47730	chr2:178602064;178602063;178602062	chr2:179466791;179466790;179466789
N2B	9338	28237;28238;28239	chr2:178602064;178602063;178602062	chr2:179466791;179466790;179466789
Novex-1	9463	28612;28613;28614	chr2:178602064;178602063;178602062	chr2:179466791;179466790;179466789
Novex-2	9530	28813;28814;28815	chr2:178602064;178602063;178602062	chr2:179466791;179466790;179466789
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-115
• Domain position: 22
• Structural Position: 38
• Q(SASA): 0.7095
• 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
K/E	None	None	0.722	N	0.429	0.24	0.305410167561	gnomAD-4.0.0	1.59329E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.02847E-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
K/A	0.4916	ambiguous	0.5113	ambiguous	-0.004	Destabilizing	0.415	N	0.432	neutral	None	None	None	None	I
K/C	0.6959	likely_pathogenic	0.6609	pathogenic	-0.54	Destabilizing	0.996	D	0.513	neutral	None	None	None	None	I
K/D	0.8031	likely_pathogenic	0.8424	pathogenic	-0.275	Destabilizing	0.775	D	0.419	neutral	None	None	None	None	I
K/E	0.3009	likely_benign	0.356	ambiguous	-0.278	Destabilizing	0.722	D	0.429	neutral	N	0.476144682	None	None	I
K/F	0.8119	likely_pathogenic	0.82	pathogenic	-0.325	Destabilizing	0.987	D	0.499	neutral	None	None	None	None	I
K/G	0.6362	likely_pathogenic	0.6572	pathogenic	-0.141	Destabilizing	0.633	D	0.435	neutral	None	None	None	None	I
K/H	0.312	likely_benign	0.3123	benign	-0.213	Destabilizing	0.989	D	0.445	neutral	None	None	None	None	I
K/I	0.4464	ambiguous	0.4887	ambiguous	0.274	Stabilizing	0.923	D	0.499	neutral	None	None	None	None	I
K/L	0.4983	ambiguous	0.5118	ambiguous	0.274	Stabilizing	0.775	D	0.454	neutral	None	None	None	None	I
K/M	0.3179	likely_benign	0.3444	ambiguous	-0.16	Destabilizing	0.995	D	0.449	neutral	N	0.519668959	None	None	I
K/N	0.5628	ambiguous	0.6208	pathogenic	-0.105	Destabilizing	0.722	D	0.409	neutral	N	0.483846359	None	None	I
K/P	0.9719	likely_pathogenic	0.9782	pathogenic	0.205	Stabilizing	0.961	D	0.429	neutral	None	None	None	None	I
K/Q	0.1705	likely_benign	0.1819	benign	-0.216	Destabilizing	0.901	D	0.434	neutral	N	0.488825977	None	None	I
K/R	0.0757	likely_benign	0.0751	benign	-0.141	Destabilizing	0.008	N	0.149	neutral	N	0.464314322	None	None	I
K/S	0.4807	ambiguous	0.5066	ambiguous	-0.46	Destabilizing	0.044	N	0.23	neutral	None	None	None	None	I
K/T	0.1791	likely_benign	0.1995	benign	-0.34	Destabilizing	0.034	N	0.231	neutral	N	0.413981502	None	None	I
K/V	0.4248	ambiguous	0.4473	ambiguous	0.205	Stabilizing	0.923	D	0.417	neutral	None	None	None	None	I
K/W	0.7752	likely_pathogenic	0.7785	pathogenic	-0.436	Destabilizing	0.996	D	0.611	neutral	None	None	None	None	I
K/Y	0.6933	likely_pathogenic	0.7079	pathogenic	-0.082	Destabilizing	0.987	D	0.491	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.