TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17602	53029;53030;53031	chr2:178607983;178607982;178607981	chr2:179472710;179472709;179472708
N2AB	15961	48106;48107;48108	chr2:178607983;178607982;178607981	chr2:179472710;179472709;179472708
N2A	15034	45325;45326;45327	chr2:178607983;178607982;178607981	chr2:179472710;179472709;179472708
N2B	8537	25834;25835;25836	chr2:178607983;178607982;178607981	chr2:179472710;179472709;179472708
Novex-1	8662	26209;26210;26211	chr2:178607983;178607982;178607981	chr2:179472710;179472709;179472708
Novex-2	8729	26410;26411;26412	chr2:178607983;178607982;178607981	chr2:179472710;179472709;179472708
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-16
• Domain position: 34
• Structural Position: 36
• Q(SASA): 0.3714
• 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
V/I	None	None	None	N	0.059	0.185	0.132336055621	gnomAD-4.0.0	6.84508E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	1.73671E-04	0	0	0
V/L	rs771120988	-0.153	None	N	0.069	0.174	0.159798565429	gnomAD-2.1.1	8.06E-06	None	None	None	None	I	None	0	5.8E-05	None	0	0	None	0	None	0	0	0
V/L	rs771120988	-0.153	None	N	0.069	0.174	0.159798565429	gnomAD-4.0.0	1.36902E-06	None	None	None	None	I	None	0	4.47507E-05	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
V/A	0.1097	likely_benign	0.0917	benign	-0.507	Destabilizing	None	N	0.094	neutral	N	0.453603391	None	None	I
V/C	0.5401	ambiguous	0.4734	ambiguous	-0.651	Destabilizing	0.497	N	0.315	neutral	None	None	None	None	I
V/D	0.3241	likely_benign	0.2582	benign	-0.367	Destabilizing	0.033	N	0.485	neutral	N	0.413447492	None	None	I
V/E	0.235	likely_benign	0.1852	benign	-0.461	Destabilizing	0.044	N	0.409	neutral	None	None	None	None	I
V/F	0.1266	likely_benign	0.0987	benign	-0.599	Destabilizing	None	N	0.209	neutral	N	0.458953283	None	None	I
V/G	0.2062	likely_benign	0.1616	benign	-0.667	Destabilizing	0.007	N	0.374	neutral	N	0.448082928	None	None	I
V/H	0.3506	ambiguous	0.2809	benign	-0.162	Destabilizing	0.497	N	0.385	neutral	None	None	None	None	I
V/I	0.0608	likely_benign	0.0578	benign	-0.226	Destabilizing	None	N	0.059	neutral	N	0.372238375	None	None	I
V/K	0.2149	likely_benign	0.1704	benign	-0.537	Destabilizing	0.044	N	0.411	neutral	None	None	None	None	I
V/L	0.0934	likely_benign	0.0799	benign	-0.226	Destabilizing	None	N	0.069	neutral	N	0.358999719	None	None	I
V/M	0.0973	likely_benign	0.0817	benign	-0.38	Destabilizing	0.001	N	0.219	neutral	None	None	None	None	I
V/N	0.1915	likely_benign	0.1513	benign	-0.271	Destabilizing	0.044	N	0.511	neutral	None	None	None	None	I
V/P	0.639	likely_pathogenic	0.5913	pathogenic	-0.284	Destabilizing	0.085	N	0.485	neutral	None	None	None	None	I
V/Q	0.2126	likely_benign	0.176	benign	-0.496	Destabilizing	0.044	N	0.466	neutral	None	None	None	None	I
V/R	0.1667	likely_benign	0.135	benign	-0.008	Destabilizing	0.044	N	0.515	neutral	None	None	None	None	I
V/S	0.1264	likely_benign	0.1025	benign	-0.646	Destabilizing	0.009	N	0.379	neutral	None	None	None	None	I
V/T	0.0765	likely_benign	0.0645	benign	-0.638	Destabilizing	None	N	0.063	neutral	None	None	None	None	I
V/W	0.6251	likely_pathogenic	0.5074	ambiguous	-0.686	Destabilizing	0.788	D	0.373	neutral	None	None	None	None	I
V/Y	0.405	ambiguous	0.3385	benign	-0.396	Destabilizing	0.022	N	0.408	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.