TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25900	77923;77924;77925	chr2:178568434;178568433;178568432	chr2:179433161;179433160;179433159
N2AB	24259	73000;73001;73002	chr2:178568434;178568433;178568432	chr2:179433161;179433160;179433159
N2A	23332	70219;70220;70221	chr2:178568434;178568433;178568432	chr2:179433161;179433160;179433159
N2B	16835	50728;50729;50730	chr2:178568434;178568433;178568432	chr2:179433161;179433160;179433159
Novex-1	16960	51103;51104;51105	chr2:178568434;178568433;178568432	chr2:179433161;179433160;179433159
Novex-2	17027	51304;51305;51306	chr2:178568434;178568433;178568432	chr2:179433161;179433160;179433159
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Fn3-76
• Domain position: 11
• Structural Position: 12
• Q(SASA): 0.1876
• 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
F/S	rs1189958133	None	0.912	N	0.646	0.47	0.644325926208	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
F/S	rs1189958133	None	0.912	N	0.646	0.47	0.644325926208	gnomAD-4.0.0	6.57618E-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
F/A	0.5628	ambiguous	0.6199	pathogenic	-2.429	Highly Destabilizing	0.737	D	0.478	neutral	None	None	None	None	N
F/C	0.2968	likely_benign	0.3431	ambiguous	-1.908	Destabilizing	0.998	D	0.702	prob.neutral	N	0.473347475	None	None	N
F/D	0.9554	likely_pathogenic	0.9689	pathogenic	-1.487	Destabilizing	0.993	D	0.748	deleterious	None	None	None	None	N
F/E	0.9416	likely_pathogenic	0.9595	pathogenic	-1.304	Destabilizing	0.993	D	0.748	deleterious	None	None	None	None	N
F/G	0.8769	likely_pathogenic	0.9061	pathogenic	-2.858	Highly Destabilizing	0.932	D	0.72	prob.delet.	None	None	None	None	N
F/H	0.8149	likely_pathogenic	0.8526	pathogenic	-1.23	Destabilizing	0.998	D	0.667	neutral	None	None	None	None	N
F/I	0.1289	likely_benign	0.1592	benign	-1.082	Destabilizing	0.028	N	0.255	neutral	N	0.411679411	None	None	N
F/K	0.9143	likely_pathogenic	0.9372	pathogenic	-1.846	Destabilizing	0.932	D	0.744	deleterious	None	None	None	None	N
F/L	0.7535	likely_pathogenic	0.8142	pathogenic	-1.082	Destabilizing	0.007	N	0.201	neutral	N	0.471919793	None	None	N
F/M	0.3365	likely_benign	0.3749	ambiguous	-1.002	Destabilizing	0.38	N	0.367	neutral	None	None	None	None	N
F/N	0.8588	likely_pathogenic	0.8973	pathogenic	-2.14	Highly Destabilizing	0.993	D	0.737	prob.delet.	None	None	None	None	N
F/P	0.9607	likely_pathogenic	0.9625	pathogenic	-1.533	Destabilizing	0.993	D	0.737	prob.delet.	None	None	None	None	N
F/Q	0.8846	likely_pathogenic	0.9184	pathogenic	-2.037	Highly Destabilizing	0.98	D	0.74	deleterious	None	None	None	None	N
F/R	0.8699	likely_pathogenic	0.906	pathogenic	-1.383	Destabilizing	0.98	D	0.737	prob.delet.	None	None	None	None	N
F/S	0.6428	likely_pathogenic	0.7263	pathogenic	-3.013	Highly Destabilizing	0.912	D	0.646	neutral	N	0.479423862	None	None	N
F/T	0.4956	ambiguous	0.5772	pathogenic	-2.713	Highly Destabilizing	0.872	D	0.625	neutral	None	None	None	None	N
F/V	0.1663	likely_benign	0.204	benign	-1.533	Destabilizing	0.028	N	0.325	neutral	N	0.390781276	None	None	N
F/W	0.4928	ambiguous	0.527	ambiguous	-0.146	Destabilizing	0.998	D	0.591	neutral	None	None	None	None	N
F/Y	0.2254	likely_benign	0.243	benign	-0.509	Destabilizing	0.969	D	0.537	neutral	N	0.494722082	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.