TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5773	17542;17543;17544	chr2:178731449;178731448;178731447	chr2:179596176;179596175;179596174
N2AB	5456	16591;16592;16593	chr2:178731449;178731448;178731447	chr2:179596176;179596175;179596174
N2A	4529	13810;13811;13812	chr2:178731449;178731448;178731447	chr2:179596176;179596175;179596174
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-41
• Domain position: 44
• Structural Position: 73
• Q(SASA): 1.028
• 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
D/E	rs760724229	0.12	0.967	N	0.397	0.14	0.132336055621	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	5.57E-05	None	0	None	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
D/A	0.2111	likely_benign	0.2534	benign	-0.221	Destabilizing	0.134	N	0.294	neutral	N	0.498980603	None	None	N
D/C	0.7184	likely_pathogenic	0.7514	pathogenic	0.157	Stabilizing	0.999	D	0.427	neutral	None	None	None	None	N
D/E	0.2601	likely_benign	0.3072	benign	-0.296	Destabilizing	0.967	D	0.397	neutral	N	0.508157447	None	None	N
D/F	0.6699	likely_pathogenic	0.7436	pathogenic	-0.306	Destabilizing	0.997	D	0.411	neutral	None	None	None	None	N
D/G	0.1303	likely_benign	0.1366	benign	-0.398	Destabilizing	0.035	N	0.331	neutral	N	0.465595961	None	None	N
D/H	0.3894	ambiguous	0.4452	ambiguous	-0.17	Destabilizing	0.999	D	0.383	neutral	N	0.469823578	None	None	N
D/I	0.5653	likely_pathogenic	0.6665	pathogenic	0.19	Stabilizing	0.991	D	0.415	neutral	None	None	None	None	N
D/K	0.4769	ambiguous	0.5259	ambiguous	0.364	Stabilizing	0.884	D	0.367	neutral	None	None	None	None	N
D/L	0.4974	ambiguous	0.5769	pathogenic	0.19	Stabilizing	0.982	D	0.413	neutral	None	None	None	None	N
D/M	0.6782	likely_pathogenic	0.7439	pathogenic	0.361	Stabilizing	0.999	D	0.415	neutral	None	None	None	None	N
D/N	0.102	likely_benign	0.1137	benign	0.157	Stabilizing	0.92	D	0.403	neutral	N	0.479354692	None	None	N
D/P	0.8835	likely_pathogenic	0.9063	pathogenic	0.075	Stabilizing	0.991	D	0.387	neutral	None	None	None	None	N
D/Q	0.4914	ambiguous	0.5452	ambiguous	0.171	Stabilizing	0.991	D	0.372	neutral	None	None	None	None	N
D/R	0.5212	ambiguous	0.578	pathogenic	0.466	Stabilizing	0.321	N	0.359	neutral	None	None	None	None	N
D/S	0.1348	likely_benign	0.1487	benign	0.05	Stabilizing	0.373	N	0.229	neutral	None	None	None	None	N
D/T	0.2499	likely_benign	0.272	benign	0.183	Stabilizing	0.884	D	0.393	neutral	None	None	None	None	N
D/V	0.3344	likely_benign	0.4233	ambiguous	0.075	Stabilizing	0.976	D	0.415	neutral	N	0.481686862	None	None	N
D/W	0.9059	likely_pathogenic	0.9255	pathogenic	-0.228	Destabilizing	0.999	D	0.551	neutral	None	None	None	None	N
D/Y	0.2976	likely_benign	0.3635	ambiguous	-0.081	Destabilizing	0.996	D	0.41	neutral	N	0.470330557	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.