TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8102	24529;24530;24531	chr2:178718896;178718895;178718894	chr2:179583623;179583622;179583621
N2AB	7785	23578;23579;23580	chr2:178718896;178718895;178718894	chr2:179583623;179583622;179583621
N2A	6858	20797;20798;20799	chr2:178718896;178718895;178718894	chr2:179583623;179583622;179583621
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-66
• Domain position: 25
• Structural Position: 38
• Q(SASA): 0.5291
• 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	rs748064860	-0.15	None	N	0.072	0.088	0.294206760003	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	6.48E-05	0	None	0	0	None	0	None	0	0	0
R/K	rs748064860	-0.15	None	N	0.072	0.088	0.294206760003	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
R/K	rs748064860	-0.15	None	N	0.072	0.088	0.294206760003	gnomAD-4.0.0	6.57514E-06	None	None	None	None	N	None	2.41441E-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
R/A	0.2983	likely_benign	0.2573	benign	-0.5	Destabilizing	0.007	N	0.143	neutral	None	None	None	None	N
R/C	0.2223	likely_benign	0.1698	benign	-0.647	Destabilizing	0.676	D	0.175	neutral	None	None	None	None	N
R/D	0.6672	likely_pathogenic	0.6086	pathogenic	0.059	Stabilizing	0.072	N	0.22	neutral	None	None	None	None	N
R/E	0.2979	likely_benign	0.2747	benign	0.174	Stabilizing	0.016	N	0.159	neutral	None	None	None	None	N
R/F	0.5101	ambiguous	0.4626	ambiguous	-0.54	Destabilizing	0.356	N	0.216	neutral	None	None	None	None	N
R/G	0.1948	likely_benign	0.1669	benign	-0.757	Destabilizing	0.012	N	0.205	neutral	N	0.520514321	None	None	N
R/H	0.1032	likely_benign	0.0914	benign	-1.198	Destabilizing	0.356	N	0.277	neutral	None	None	None	None	N
R/I	0.2456	likely_benign	0.2322	benign	0.169	Stabilizing	0.055	N	0.275	neutral	N	0.514433711	None	None	N
R/K	0.0822	likely_benign	0.0833	benign	-0.405	Destabilizing	None	N	0.072	neutral	N	0.424235781	None	None	N
R/L	0.2416	likely_benign	0.2096	benign	0.169	Stabilizing	0.031	N	0.23	neutral	None	None	None	None	N
R/M	0.2313	likely_benign	0.2221	benign	-0.311	Destabilizing	0.628	D	0.223	neutral	None	None	None	None	N
R/N	0.4907	ambiguous	0.4499	ambiguous	-0.194	Destabilizing	0.016	N	0.152	neutral	None	None	None	None	N
R/P	0.9049	likely_pathogenic	0.8716	pathogenic	-0.033	Destabilizing	0.072	N	0.244	neutral	None	None	None	None	N
R/Q	0.0973	likely_benign	0.0913	benign	-0.262	Destabilizing	0.038	N	0.159	neutral	None	None	None	None	N
R/S	0.3367	likely_benign	0.2928	benign	-0.805	Destabilizing	None	N	0.133	neutral	N	0.463138099	None	None	N
R/T	0.1544	likely_benign	0.1426	benign	-0.514	Destabilizing	None	N	0.136	neutral	N	0.468063916	None	None	N
R/V	0.3288	likely_benign	0.2997	benign	-0.033	Destabilizing	0.072	N	0.241	neutral	None	None	None	None	N
R/W	0.1802	likely_benign	0.155	benign	-0.406	Destabilizing	0.864	D	0.188	neutral	None	None	None	None	N
R/Y	0.4143	ambiguous	0.3526	ambiguous	-0.053	Destabilizing	0.356	N	0.221	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.