TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6898	20917;20918;20919	chr2:178725512;178725511;178725510	chr2:179590239;179590238;179590237
N2AB	6581	19966;19967;19968	chr2:178725512;178725511;178725510	chr2:179590239;179590238;179590237
N2A	5654	17185;17186;17187	chr2:178725512;178725511;178725510	chr2:179590239;179590238;179590237
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: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Ig-53
• Domain position: 45
• Structural Position: 73
• Q(SASA): 0.2122
• 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
S/G	rs878854291	None	0.005	N	0.119	0.098	0.0806252709748	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
S/G	rs878854291	None	0.005	N	0.119	0.098	0.0806252709748	gnomAD-4.0.0	8.05822E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.01736E-05	0	1.60149E-05
S/R	rs878854291	None	0.988	N	0.318	0.282	0.281780670237	gnomAD-4.0.0	1.59237E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86026E-06	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
S/A	0.1618	likely_benign	0.1481	benign	-0.207	Destabilizing	0.079	N	0.156	neutral	None	None	None	None	N
S/C	0.3218	likely_benign	0.3076	benign	-0.281	Destabilizing	0.999	D	0.296	neutral	N	0.50875802	None	None	N
S/D	0.4084	ambiguous	0.3711	ambiguous	0.02	Stabilizing	0.046	N	0.191	neutral	None	None	None	None	N
S/E	0.7148	likely_pathogenic	0.692	pathogenic	-0.084	Destabilizing	0.884	D	0.33	neutral	None	None	None	None	N
S/F	0.4885	ambiguous	0.4686	ambiguous	-0.845	Destabilizing	0.997	D	0.374	neutral	None	None	None	None	N
S/G	0.1136	likely_benign	0.1008	benign	-0.296	Destabilizing	0.005	N	0.119	neutral	N	0.484203152	None	None	N
S/H	0.6208	likely_pathogenic	0.5983	pathogenic	-0.762	Destabilizing	0.997	D	0.293	neutral	None	None	None	None	N
S/I	0.5834	likely_pathogenic	0.5525	ambiguous	-0.109	Destabilizing	0.988	D	0.396	neutral	N	0.497148225	None	None	N
S/K	0.8564	likely_pathogenic	0.8526	pathogenic	-0.505	Destabilizing	0.969	D	0.328	neutral	None	None	None	None	N
S/L	0.2338	likely_benign	0.2147	benign	-0.109	Destabilizing	0.939	D	0.419	neutral	None	None	None	None	N
S/M	0.4083	ambiguous	0.3646	ambiguous	0.018	Stabilizing	0.999	D	0.291	neutral	None	None	None	None	N
S/N	0.1916	likely_benign	0.1535	benign	-0.209	Destabilizing	0.92	D	0.382	neutral	N	0.469418731	None	None	N
S/P	0.8122	likely_pathogenic	0.8368	pathogenic	-0.114	Destabilizing	0.991	D	0.319	neutral	None	None	None	None	N
S/Q	0.7686	likely_pathogenic	0.7427	pathogenic	-0.454	Destabilizing	0.991	D	0.338	neutral	None	None	None	None	N
S/R	0.8253	likely_pathogenic	0.8261	pathogenic	-0.27	Destabilizing	0.988	D	0.318	neutral	N	0.478030012	None	None	N
S/T	0.1228	likely_benign	0.1018	benign	-0.296	Destabilizing	0.92	D	0.375	neutral	N	0.474293803	None	None	N
S/V	0.534	ambiguous	0.4829	ambiguous	-0.114	Destabilizing	0.939	D	0.411	neutral	None	None	None	None	N
S/W	0.5866	likely_pathogenic	0.6075	pathogenic	-0.905	Destabilizing	0.999	D	0.477	neutral	None	None	None	None	N
S/Y	0.3954	ambiguous	0.4044	ambiguous	-0.608	Destabilizing	0.997	D	0.373	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.