TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8795	26608;26609;26610	chr2:178714391;178714390;178714389	chr2:179579118;179579117;179579116
N2AB	8478	25657;25658;25659	chr2:178714391;178714390;178714389	chr2:179579118;179579117;179579116
N2A	7551	22876;22877;22878	chr2:178714391;178714390;178714389	chr2:179579118;179579117;179579116
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: Q
• RefSeq wild type transcript codon: CAG
• RefSeq wild type template codon: GTC
• Domain: Ig-73
• Domain position: 60
• Structural Position: 139
• Q(SASA): 0.5322
• 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
Q/E	None	None	0.071	N	0.349	0.121	0.276482976112	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05
Q/R	None	None	0.046	N	0.433	0.123	0.171388866994	gnomAD-4.0.0	1.59134E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85847E-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
Q/A	0.2122	likely_benign	0.2398	benign	-0.965	Destabilizing	0.328	N	0.451	neutral	None	None	None	None	N
Q/C	0.4038	ambiguous	0.4803	ambiguous	-0.52	Destabilizing	0.967	D	0.505	neutral	None	None	None	None	N
Q/D	0.3801	ambiguous	0.4299	ambiguous	-1.698	Destabilizing	0.262	N	0.395	neutral	None	None	None	None	N
Q/E	0.0952	likely_benign	0.1007	benign	-1.433	Destabilizing	0.071	N	0.349	neutral	N	0.504427361	None	None	N
Q/F	0.4376	ambiguous	0.4873	ambiguous	-0.387	Destabilizing	0.824	D	0.528	neutral	None	None	None	None	N
Q/G	0.247	likely_benign	0.2895	benign	-1.43	Destabilizing	0.542	D	0.525	neutral	None	None	None	None	N
Q/H	0.1236	likely_benign	0.1368	benign	-1.093	Destabilizing	0.001	N	0.314	neutral	N	0.506891663	None	None	N
Q/I	0.2641	likely_benign	0.2974	benign	0.297	Stabilizing	0.006	N	0.461	neutral	None	None	None	None	N
Q/K	0.0937	likely_benign	0.1008	benign	-0.471	Destabilizing	None	N	0.239	neutral	N	0.457809637	None	None	N
Q/L	0.1102	likely_benign	0.1216	benign	0.297	Stabilizing	0.068	N	0.464	neutral	N	0.516895226	None	None	N
Q/M	0.3235	likely_benign	0.3516	ambiguous	0.525	Stabilizing	0.77	D	0.449	neutral	None	None	None	None	N
Q/N	0.2423	likely_benign	0.2677	benign	-1.359	Destabilizing	0.151	N	0.389	neutral	None	None	None	None	N
Q/P	0.6067	likely_pathogenic	0.6729	pathogenic	-0.095	Destabilizing	0.352	N	0.512	neutral	N	0.516812412	None	None	N
Q/R	0.0791	likely_benign	0.0863	benign	-0.656	Destabilizing	0.046	N	0.433	neutral	N	0.483281298	None	None	N
Q/S	0.2102	likely_benign	0.2305	benign	-1.57	Destabilizing	0.328	N	0.407	neutral	None	None	None	None	N
Q/T	0.1635	likely_benign	0.1872	benign	-1.098	Destabilizing	0.044	N	0.493	neutral	None	None	None	None	N
Q/V	0.201	likely_benign	0.2235	benign	-0.095	Destabilizing	0.028	N	0.477	neutral	None	None	None	None	N
Q/W	0.3048	likely_benign	0.3606	ambiguous	-0.398	Destabilizing	0.993	D	0.51	neutral	None	None	None	None	N
Q/Y	0.2512	likely_benign	0.2818	benign	-0.036	Destabilizing	0.536	D	0.553	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.