TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6529	19810;19811;19812	chr2:178728239;178728238;178728237	chr2:179592966;179592965;179592964
N2AB	6212	18859;18860;18861	chr2:178728239;178728238;178728237	chr2:179592966;179592965;179592964
N2A	5285	16078;16079;16080	chr2:178728239;178728238;178728237	chr2:179592966;179592965;179592964
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: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-49
• Domain position: 49
• Structural Position: 123
• Q(SASA): 0.2717
• 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
L/F	rs758456020	-1.228	0.934	N	0.526	0.323	None	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	0	None	6.54E-05	None	0	8.93E-06	0
L/F	rs758456020	-1.228	0.934	N	0.526	0.323	None	gnomAD-4.0.0	7.9629E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.72118E-06	2.86673E-05	3.02755E-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
L/A	0.1451	likely_benign	0.1775	benign	-1.937	Destabilizing	0.525	D	0.451	neutral	None	None	None	None	N
L/C	0.3947	ambiguous	0.4479	ambiguous	-1.161	Destabilizing	0.998	D	0.559	neutral	None	None	None	None	N
L/D	0.4831	ambiguous	0.567	pathogenic	-1.466	Destabilizing	0.949	D	0.646	neutral	None	None	None	None	N
L/E	0.233	likely_benign	0.2844	benign	-1.351	Destabilizing	0.949	D	0.635	neutral	None	None	None	None	N
L/F	0.1026	likely_benign	0.117	benign	-1.161	Destabilizing	0.934	D	0.526	neutral	N	0.42864431	None	None	N
L/G	0.3476	ambiguous	0.4113	ambiguous	-2.382	Highly Destabilizing	0.728	D	0.61	neutral	None	None	None	None	N
L/H	0.1461	likely_benign	0.1723	benign	-1.679	Destabilizing	0.997	D	0.621	neutral	N	0.517034086	None	None	N
L/I	0.0726	likely_benign	0.0772	benign	-0.723	Destabilizing	0.051	N	0.283	neutral	N	0.370652012	None	None	N
L/K	0.183	likely_benign	0.2068	benign	-1.325	Destabilizing	0.842	D	0.603	neutral	None	None	None	None	N
L/M	0.0903	likely_benign	0.0912	benign	-0.586	Destabilizing	0.325	N	0.324	neutral	None	None	None	None	N
L/N	0.2564	likely_benign	0.3033	benign	-1.338	Destabilizing	0.949	D	0.634	neutral	None	None	None	None	N
L/P	0.1521	likely_benign	0.2158	benign	-1.1	Destabilizing	0.012	N	0.427	neutral	N	0.447808861	None	None	N
L/Q	0.1172	likely_benign	0.1407	benign	-1.348	Destabilizing	0.974	D	0.613	neutral	None	None	None	None	N
L/R	0.1442	likely_benign	0.1679	benign	-0.929	Destabilizing	0.934	D	0.609	neutral	N	0.46702934	None	None	N
L/S	0.1609	likely_benign	0.2027	benign	-2.049	Highly Destabilizing	0.067	N	0.38	neutral	None	None	None	None	N
L/T	0.1156	likely_benign	0.1359	benign	-1.798	Destabilizing	0.728	D	0.494	neutral	None	None	None	None	N
L/V	0.0726	likely_benign	0.0783	benign	-1.1	Destabilizing	0.454	N	0.446	neutral	N	0.399990698	None	None	N
L/W	0.1684	likely_benign	0.1827	benign	-1.383	Destabilizing	0.998	D	0.631	neutral	None	None	None	None	N
L/Y	0.2497	likely_benign	0.2743	benign	-1.098	Destabilizing	0.991	D	0.579	neutral	None	None	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.