TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8962	27109;27110;27111	chr2:178713250;178713249;178713248	chr2:179577977;179577976;179577975
N2AB	8645	26158;26159;26160	chr2:178713250;178713249;178713248	chr2:179577977;179577976;179577975
N2A	7718	23377;23378;23379	chr2:178713250;178713249;178713248	chr2:179577977;179577976;179577975
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: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-75
• Domain position: 37
• Structural Position: 51
• Q(SASA): 0.6622
• 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
E/D	rs2076925397	None	None	N	0.101	0.117	0.0611884634855	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
E/D	rs2076925397	None	None	N	0.101	0.117	0.0611884634855	gnomAD-4.0.0	6.57263E-06	None	None	None	None	N	None	0	6.55136E-05	None	0	0	None	0	0	0	0	0
E/V	None	None	0.055	N	0.425	0.098	0.316788114976	gnomAD-4.0.0	3.18641E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	2.4108E-04	2.86113E-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
E/A	0.1208	likely_benign	0.1225	benign	-0.611	Destabilizing	0.012	N	0.327	neutral	N	0.475140951	None	None	N
E/C	0.6197	likely_pathogenic	0.6065	pathogenic	-0.058	Destabilizing	0.864	D	0.343	neutral	None	None	None	None	N
E/D	0.0959	likely_benign	0.0853	benign	-0.482	Destabilizing	None	N	0.101	neutral	N	0.348286001	None	None	N
E/F	0.6316	likely_pathogenic	0.6281	pathogenic	-0.498	Destabilizing	0.628	D	0.368	neutral	None	None	None	None	N
E/G	0.0708	likely_benign	0.0733	benign	-0.84	Destabilizing	None	N	0.165	neutral	N	0.436889207	None	None	N
E/H	0.2615	likely_benign	0.2479	benign	-0.449	Destabilizing	0.356	N	0.287	neutral	None	None	None	None	N
E/I	0.4448	ambiguous	0.4863	ambiguous	-0.029	Destabilizing	0.356	N	0.396	neutral	None	None	None	None	N
E/K	0.0769	likely_benign	0.0907	benign	0.036	Stabilizing	None	N	0.121	neutral	N	0.458363345	None	None	N
E/L	0.3342	likely_benign	0.3515	ambiguous	-0.029	Destabilizing	0.072	N	0.447	neutral	None	None	None	None	N
E/M	0.375	ambiguous	0.401	ambiguous	0.272	Stabilizing	0.628	D	0.339	neutral	None	None	None	None	N
E/N	0.1305	likely_benign	0.1148	benign	-0.215	Destabilizing	None	N	0.111	neutral	None	None	None	None	N
E/P	0.8174	likely_pathogenic	0.8215	pathogenic	-0.203	Destabilizing	0.136	N	0.415	neutral	None	None	None	None	N
E/Q	0.0887	likely_benign	0.0884	benign	-0.177	Destabilizing	0.029	N	0.263	neutral	N	0.47531431	None	None	N
E/R	0.116	likely_benign	0.1151	benign	0.238	Stabilizing	0.038	N	0.229	neutral	None	None	None	None	N
E/S	0.1305	likely_benign	0.1248	benign	-0.426	Destabilizing	0.016	N	0.175	neutral	None	None	None	None	N
E/T	0.235	likely_benign	0.2663	benign	-0.244	Destabilizing	0.031	N	0.339	neutral	None	None	None	None	N
E/V	0.2769	likely_benign	0.3053	benign	-0.203	Destabilizing	0.055	N	0.425	neutral	N	0.485800662	None	None	N
E/W	0.7498	likely_pathogenic	0.7502	pathogenic	-0.332	Destabilizing	0.864	D	0.362	neutral	None	None	None	None	N
E/Y	0.4349	ambiguous	0.4313	ambiguous	-0.261	Destabilizing	0.628	D	0.362	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.