TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9498	28717;28718;28719	chr2:178709827;178709826;178709825	chr2:179574554;179574553;179574552
N2AB	9181	27766;27767;27768	chr2:178709827;178709826;178709825	chr2:179574554;179574553;179574552
N2A	8254	24985;24986;24987	chr2:178709827;178709826;178709825	chr2:179574554;179574553;179574552
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: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Ig-81
• Domain position: 6
• Structural Position: 7
• Q(SASA): 0.3884
• 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
R/G	rs757471312	-1.169	0.024	None	0.31	0.171	0.471620082127	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	1.29282E-04	0	None	0	0	None	0	None	0	0	0
R/G	rs757471312	-1.169	0.024	None	0.31	0.171	0.471620082127	gnomAD-4.0.0	3.18919E-06	None	None	None	None	N	None	1.13507E-04	0	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
R/A	0.2911	likely_benign	0.486	ambiguous	-0.099	Destabilizing	0.007	N	0.255	neutral	None	None	None	None	N
R/C	0.2892	likely_benign	0.5241	ambiguous	-0.334	Destabilizing	0.864	D	0.307	neutral	None	None	None	None	N
R/D	0.5934	likely_pathogenic	0.7587	pathogenic	-0.067	Destabilizing	0.031	N	0.336	neutral	None	None	None	None	N
R/E	0.3142	likely_benign	0.4039	ambiguous	0.027	Stabilizing	0.007	N	0.134	neutral	None	None	None	None	N
R/F	0.509	ambiguous	0.7589	pathogenic	-0.258	Destabilizing	0.628	D	0.34	neutral	None	None	None	None	N
R/G	0.2057	likely_benign	0.2156	benign	-0.315	Destabilizing	0.024	N	0.31	neutral	None	None	None	None	N
R/H	0.1346	likely_benign	0.2447	benign	-0.889	Destabilizing	0.356	N	0.268	neutral	None	None	None	None	N
R/I	0.2448	likely_benign	0.439	ambiguous	0.446	Stabilizing	0.106	N	0.399	neutral	None	None	None	None	N
R/K	0.0581	likely_benign	0.0509	benign	-0.115	Destabilizing	None	N	0.087	neutral	None	None	None	None	N
R/L	0.1921	likely_benign	0.358	ambiguous	0.446	Stabilizing	0.031	N	0.31	neutral	None	None	None	None	N
R/M	0.1978	likely_benign	0.3433	ambiguous	-0.125	Destabilizing	0.628	D	0.322	neutral	None	None	None	None	N
R/N	0.3893	ambiguous	0.5655	pathogenic	-0.04	Destabilizing	0.031	N	0.174	neutral	None	None	None	None	N
R/P	0.2332	likely_benign	0.3717	ambiguous	0.285	Stabilizing	0.136	N	0.357	neutral	None	None	None	None	N
R/Q	0.1058	likely_benign	0.1586	benign	-0.054	Destabilizing	0.016	N	0.179	neutral	None	None	None	None	N
R/S	0.3554	ambiguous	0.5724	pathogenic	-0.396	Destabilizing	0.012	N	0.315	neutral	None	None	None	None	N
R/T	0.1926	likely_benign	0.3455	ambiguous	-0.148	Destabilizing	0.024	N	0.307	neutral	None	None	None	None	N
R/V	0.2901	likely_benign	0.4781	ambiguous	0.285	Stabilizing	0.072	N	0.381	neutral	None	None	None	None	N
R/W	0.2517	likely_benign	0.4598	ambiguous	-0.311	Destabilizing	0.864	D	0.31	neutral	None	None	None	None	N
R/Y	0.3851	ambiguous	0.6148	pathogenic	0.093	Stabilizing	0.356	N	0.363	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.