TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18862	56809;56810;56811	chr2:178599209;178599208;178599207	chr2:179463936;179463935;179463934
N2AB	17221	51886;51887;51888	chr2:178599209;178599208;178599207	chr2:179463936;179463935;179463934
N2A	16294	49105;49106;49107	chr2:178599209;178599208;178599207	chr2:179463936;179463935;179463934
N2B	9797	29614;29615;29616	chr2:178599209;178599208;178599207	chr2:179463936;179463935;179463934
Novex-1	9922	29989;29990;29991	chr2:178599209;178599208;178599207	chr2:179463936;179463935;179463934
Novex-2	9989	30190;30191;30192	chr2:178599209;178599208;178599207	chr2:179463936;179463935;179463934
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAG
• RefSeq wild type template codon: GTC
• Domain: Fn3-24
• Domain position: 79
• Structural Position: 111
• Q(SASA): 0.3457
• 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
Q/H	None	None	0.667	N	0.563	0.224	0.263140351381	gnomAD-4.0.0	7.30315E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	1.77217E-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
Q/A	0.5217	ambiguous	0.4756	ambiguous	-0.277	Destabilizing	0.157	N	0.579	neutral	None	None	None	None	I
Q/C	0.8219	likely_pathogenic	0.788	pathogenic	-0.559	Destabilizing	0.968	D	0.751	deleterious	None	None	None	None	I
Q/D	0.9589	likely_pathogenic	0.9498	pathogenic	-2.305	Highly Destabilizing	0.157	N	0.515	neutral	None	None	None	None	I
Q/E	0.1189	likely_benign	0.1172	benign	-2.128	Highly Destabilizing	0.001	N	0.178	neutral	N	0.395691238	None	None	I
Q/F	0.9567	likely_pathogenic	0.9445	pathogenic	-0.338	Destabilizing	0.89	D	0.769	deleterious	None	None	None	None	I
Q/G	0.7448	likely_pathogenic	0.7031	pathogenic	-0.616	Destabilizing	0.272	N	0.649	neutral	None	None	None	None	I
Q/H	0.7678	likely_pathogenic	0.7346	pathogenic	-0.792	Destabilizing	0.667	D	0.563	neutral	N	0.497316883	None	None	I
Q/I	0.689	likely_pathogenic	0.6509	pathogenic	0.585	Stabilizing	0.726	D	0.783	deleterious	None	None	None	None	I
Q/K	0.2547	likely_benign	0.2333	benign	-0.286	Destabilizing	0.055	N	0.523	neutral	N	0.467340692	None	None	I
Q/L	0.5315	ambiguous	0.4627	ambiguous	0.585	Stabilizing	0.22	N	0.664	neutral	N	0.489676047	None	None	I
Q/M	0.5971	likely_pathogenic	0.5439	ambiguous	0.704	Stabilizing	0.89	D	0.566	neutral	None	None	None	None	I
Q/N	0.8442	likely_pathogenic	0.8215	pathogenic	-1.183	Destabilizing	0.272	N	0.528	neutral	None	None	None	None	I
Q/P	0.9751	likely_pathogenic	0.9692	pathogenic	0.328	Stabilizing	0.667	D	0.698	prob.neutral	N	0.486043226	None	None	I
Q/R	0.2603	likely_benign	0.2395	benign	-0.384	Destabilizing	0.124	N	0.499	neutral	N	0.469186132	None	None	I
Q/S	0.693	likely_pathogenic	0.6427	pathogenic	-1.117	Destabilizing	0.157	N	0.5	neutral	None	None	None	None	I
Q/T	0.588	likely_pathogenic	0.5328	ambiguous	-0.782	Destabilizing	0.272	N	0.634	neutral	None	None	None	None	I
Q/V	0.4035	ambiguous	0.3629	ambiguous	0.328	Stabilizing	0.567	D	0.695	prob.neutral	None	None	None	None	I
Q/W	0.9244	likely_pathogenic	0.9109	pathogenic	-0.597	Destabilizing	0.968	D	0.73	prob.delet.	None	None	None	None	I
Q/Y	0.9117	likely_pathogenic	0.8848	pathogenic	-0.052	Destabilizing	0.89	D	0.721	prob.delet.	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.