TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24141	72646;72647;72648	chr2:178573711;178573710;178573709	chr2:179438438;179438437;179438436
N2AB	22500	67723;67724;67725	chr2:178573711;178573710;178573709	chr2:179438438;179438437;179438436
N2A	21573	64942;64943;64944	chr2:178573711;178573710;178573709	chr2:179438438;179438437;179438436
N2B	15076	45451;45452;45453	chr2:178573711;178573710;178573709	chr2:179438438;179438437;179438436
Novex-1	15201	45826;45827;45828	chr2:178573711;178573710;178573709	chr2:179438438;179438437;179438436
Novex-2	15268	46027;46028;46029	chr2:178573711;178573710;178573709	chr2:179438438;179438437;179438436
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Fn3-63
• Domain position: 20
• Structural Position: 21
• Q(SASA): 0.1408
• 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
V/I	rs1458321606	None	0.014	N	0.446	0.041	0.33085137897	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
V/I	rs1458321606	None	0.014	N	0.446	0.041	0.33085137897	gnomAD-4.0.0	6.57635E-06	None	None	None	None	N	None	2.41359E-05	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
V/A	0.1873	likely_benign	0.1954	benign	-1.656	Destabilizing	0.489	N	0.518	neutral	N	0.483926298	None	None	N
V/C	0.5736	likely_pathogenic	0.6047	pathogenic	-1.171	Destabilizing	0.998	D	0.688	prob.neutral	None	None	None	None	N
V/D	0.4095	ambiguous	0.4454	ambiguous	-1.748	Destabilizing	0.956	D	0.745	deleterious	None	None	None	None	N
V/E	0.3358	likely_benign	0.3739	ambiguous	-1.746	Destabilizing	0.942	D	0.651	neutral	N	0.490774912	None	None	N
V/F	0.1272	likely_benign	0.1289	benign	-1.296	Destabilizing	0.956	D	0.69	prob.neutral	None	None	None	None	N
V/G	0.2417	likely_benign	0.263	benign	-1.979	Destabilizing	0.89	D	0.685	prob.neutral	N	0.477182136	None	None	N
V/H	0.4854	ambiguous	0.5012	ambiguous	-1.482	Destabilizing	0.998	D	0.779	deleterious	None	None	None	None	N
V/I	0.0693	likely_benign	0.0653	benign	-0.858	Destabilizing	0.014	N	0.446	neutral	N	0.493796575	None	None	N
V/K	0.4772	ambiguous	0.5169	ambiguous	-1.36	Destabilizing	0.956	D	0.664	neutral	None	None	None	None	N
V/L	0.1288	likely_benign	0.1224	benign	-0.858	Destabilizing	0.247	N	0.49	neutral	N	0.470746357	None	None	N
V/M	0.109	likely_benign	0.1111	benign	-0.656	Destabilizing	0.956	D	0.617	neutral	None	None	None	None	N
V/N	0.2335	likely_benign	0.2352	benign	-1.178	Destabilizing	0.956	D	0.779	deleterious	None	None	None	None	N
V/P	0.8989	likely_pathogenic	0.915	pathogenic	-1.091	Destabilizing	0.978	D	0.722	prob.delet.	None	None	None	None	N
V/Q	0.339	likely_benign	0.3607	ambiguous	-1.381	Destabilizing	0.978	D	0.746	deleterious	None	None	None	None	N
V/R	0.425	ambiguous	0.4665	ambiguous	-0.805	Destabilizing	0.956	D	0.797	deleterious	None	None	None	None	N
V/S	0.1692	likely_benign	0.1724	benign	-1.694	Destabilizing	0.16	N	0.476	neutral	None	None	None	None	N
V/T	0.1413	likely_benign	0.1439	benign	-1.589	Destabilizing	0.754	D	0.531	neutral	None	None	None	None	N
V/W	0.7364	likely_pathogenic	0.7461	pathogenic	-1.485	Destabilizing	0.998	D	0.729	prob.delet.	None	None	None	None	N
V/Y	0.4162	ambiguous	0.4162	ambiguous	-1.212	Destabilizing	0.978	D	0.711	prob.delet.	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.