TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17254	51985;51986;51987	chr2:178609550;178609549;178609548	chr2:179474277;179474276;179474275
N2AB	15613	47062;47063;47064	chr2:178609550;178609549;178609548	chr2:179474277;179474276;179474275
N2A	14686	44281;44282;44283	chr2:178609550;178609549;178609548	chr2:179474277;179474276;179474275
N2B	8189	24790;24791;24792	chr2:178609550;178609549;178609548	chr2:179474277;179474276;179474275
Novex-1	8314	25165;25166;25167	chr2:178609550;178609549;178609548	chr2:179474277;179474276;179474275
Novex-2	8381	25366;25367;25368	chr2:178609550;178609549;178609548	chr2:179474277;179474276;179474275
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-112
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.115
• 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/K	rs370986897	None	None	N	0.249	0.125	None	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
R/A	0.3178	likely_benign	0.3108	benign	-0.597	Destabilizing	None	N	0.358	neutral	None	None	None	None	N
R/C	0.2237	likely_benign	0.2527	benign	-0.653	Destabilizing	0.356	N	0.655	neutral	None	None	None	None	N
R/D	0.5132	ambiguous	0.462	ambiguous	0.021	Stabilizing	0.031	N	0.56	neutral	None	None	None	None	N
R/E	0.338	likely_benign	0.2816	benign	0.14	Stabilizing	0.016	N	0.443	neutral	None	None	None	None	N
R/F	0.5873	likely_pathogenic	0.5693	pathogenic	-0.562	Destabilizing	0.356	N	0.682	prob.neutral	None	None	None	None	N
R/G	0.1737	likely_benign	0.1673	benign	-0.883	Destabilizing	0.005	N	0.551	neutral	N	0.476165994	None	None	N
R/H	0.1314	likely_benign	0.1244	benign	-1.288	Destabilizing	0.356	N	0.603	neutral	None	None	None	None	N
R/I	0.392	ambiguous	0.3979	ambiguous	0.158	Stabilizing	0.055	N	0.617	neutral	N	0.513756133	None	None	N
R/K	0.0996	likely_benign	0.1038	benign	-0.541	Destabilizing	None	N	0.249	neutral	N	0.432214972	None	None	N
R/L	0.2813	likely_benign	0.2797	benign	0.158	Stabilizing	0.031	N	0.56	neutral	None	None	None	None	N
R/M	0.3183	likely_benign	0.3403	ambiguous	-0.252	Destabilizing	0.628	D	0.624	neutral	None	None	None	None	N
R/N	0.4089	ambiguous	0.386	ambiguous	-0.176	Destabilizing	0.031	N	0.449	neutral	None	None	None	None	N
R/P	0.2922	likely_benign	0.2538	benign	-0.073	Destabilizing	0.136	N	0.585	neutral	None	None	None	None	N
R/Q	0.1072	likely_benign	0.1033	benign	-0.296	Destabilizing	0.038	N	0.481	neutral	None	None	None	None	N
R/S	0.3658	ambiguous	0.3502	ambiguous	-0.862	Destabilizing	None	N	0.349	neutral	N	0.474645057	None	None	N
R/T	0.2332	likely_benign	0.2295	benign	-0.561	Destabilizing	0.012	N	0.516	neutral	N	0.512369267	None	None	N
R/V	0.4438	ambiguous	0.4189	ambiguous	-0.073	Destabilizing	0.016	N	0.573	neutral	None	None	None	None	N
R/W	0.2324	likely_benign	0.2548	benign	-0.331	Destabilizing	0.864	D	0.649	neutral	None	None	None	None	N
R/Y	0.4226	ambiguous	0.403	ambiguous	0.005	Stabilizing	0.356	N	0.671	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.