TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8968	27127;27128;27129	chr2:178713232;178713231;178713230	chr2:179577959;179577958;179577957
N2AB	8651	26176;26177;26178	chr2:178713232;178713231;178713230	chr2:179577959;179577958;179577957
N2A	7724	23395;23396;23397	chr2:178713232;178713231;178713230	chr2:179577959;179577958;179577957
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-75
• Domain position: 43
• Structural Position: 70
• Q(SASA): 0.8079
• 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
S/N	None	None	0.324	N	0.258	0.103	0.0920862733494	gnomAD-4.0.0	1.59227E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85954E-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	0.0767	likely_benign	0.082	benign	-0.264	Destabilizing	0.008	N	0.162	neutral	None	None	None	None	I
S/C	0.1553	likely_benign	0.1888	benign	-0.251	Destabilizing	0.975	D	0.299	neutral	N	0.511526628	None	None	I
S/D	0.3875	ambiguous	0.4548	ambiguous	0.188	Stabilizing	0.002	N	0.151	neutral	None	None	None	None	I
S/E	0.4917	ambiguous	0.5606	ambiguous	0.076	Stabilizing	0.241	N	0.187	neutral	None	None	None	None	I
S/F	0.1994	likely_benign	0.2497	benign	-1.025	Destabilizing	0.69	D	0.355	neutral	None	None	None	None	I
S/G	0.1018	likely_benign	0.106	benign	-0.303	Destabilizing	0.001	N	0.154	neutral	N	0.513417778	None	None	I
S/H	0.3696	ambiguous	0.4205	ambiguous	-0.776	Destabilizing	0.981	D	0.289	neutral	None	None	None	None	I
S/I	0.1916	likely_benign	0.228	benign	-0.292	Destabilizing	0.003	N	0.241	neutral	D	0.522383978	None	None	I
S/K	0.6222	likely_pathogenic	0.6978	pathogenic	-0.279	Destabilizing	0.388	N	0.239	neutral	None	None	None	None	I
S/L	0.0991	likely_benign	0.1202	benign	-0.292	Destabilizing	0.098	N	0.307	neutral	None	None	None	None	I
S/M	0.226	likely_benign	0.2505	benign	-0.097	Destabilizing	0.69	D	0.289	neutral	None	None	None	None	I
S/N	0.1778	likely_benign	0.2112	benign	-0.016	Destabilizing	0.324	N	0.258	neutral	N	0.45956465	None	None	I
S/P	0.1133	likely_benign	0.1248	benign	-0.259	Destabilizing	0.818	D	0.303	neutral	None	None	None	None	I
S/Q	0.5096	ambiguous	0.5642	pathogenic	-0.258	Destabilizing	0.818	D	0.245	neutral	None	None	None	None	I
S/R	0.5512	ambiguous	0.6215	pathogenic	-0.117	Destabilizing	0.627	D	0.307	neutral	N	0.520074391	None	None	I
S/T	0.0828	likely_benign	0.0944	benign	-0.138	Destabilizing	0.001	N	0.175	neutral	N	0.492618431	None	None	I
S/V	0.1843	likely_benign	0.214	benign	-0.259	Destabilizing	0.098	N	0.309	neutral	None	None	None	None	I
S/W	0.3244	likely_benign	0.3768	ambiguous	-1.078	Destabilizing	0.981	D	0.453	neutral	None	None	None	None	I
S/Y	0.1993	likely_benign	0.2389	benign	-0.767	Destabilizing	0.818	D	0.346	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.