TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17940	54043;54044;54045	chr2:178605477;178605476;178605475	chr2:179470204;179470203;179470202
N2AB	16299	49120;49121;49122	chr2:178605477;178605476;178605475	chr2:179470204;179470203;179470202
N2A	15372	46339;46340;46341	chr2:178605477;178605476;178605475	chr2:179470204;179470203;179470202
N2B	8875	26848;26849;26850	chr2:178605477;178605476;178605475	chr2:179470204;179470203;179470202
Novex-1	9000	27223;27224;27225	chr2:178605477;178605476;178605475	chr2:179470204;179470203;179470202
Novex-2	9067	27424;27425;27426	chr2:178605477;178605476;178605475	chr2:179470204;179470203;179470202
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Fn3-18
• Domain position: 79
• Structural Position: 111
• Q(SASA): 0.1257
• 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/A	None	None	0.116	N	0.181	0.214	0.477606743035	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-06	0	0
V/I	None	None	0.828	N	0.543	0.133	0.482936932564	gnomAD-4.0.0	1.59576E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86664E-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
V/A	0.4	ambiguous	0.3567	ambiguous	-2.051	Highly Destabilizing	0.116	N	0.181	neutral	N	0.508520885	None	None	N
V/C	0.7414	likely_pathogenic	0.6978	pathogenic	-1.788	Destabilizing	1.0	D	0.663	neutral	None	None	None	None	N
V/D	0.9051	likely_pathogenic	0.873	pathogenic	-2.379	Highly Destabilizing	0.994	D	0.751	deleterious	N	0.504968218	None	None	N
V/E	0.5885	likely_pathogenic	0.5526	ambiguous	-2.253	Highly Destabilizing	0.995	D	0.703	prob.neutral	None	None	None	None	N
V/F	0.2526	likely_benign	0.2555	benign	-1.339	Destabilizing	0.988	D	0.703	prob.neutral	N	0.47901315	None	None	N
V/G	0.7025	likely_pathogenic	0.6165	pathogenic	-2.494	Highly Destabilizing	0.959	D	0.71	prob.delet.	N	0.501093878	None	None	N
V/H	0.8012	likely_pathogenic	0.7622	pathogenic	-1.974	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
V/I	0.073	likely_benign	0.0782	benign	-0.859	Destabilizing	0.828	D	0.543	neutral	N	0.488510972	None	None	N
V/K	0.5616	ambiguous	0.4724	ambiguous	-1.602	Destabilizing	0.995	D	0.705	prob.neutral	None	None	None	None	N
V/L	0.3139	likely_benign	0.3064	benign	-0.859	Destabilizing	0.03	N	0.169	neutral	N	0.47918728	None	None	N
V/M	0.1898	likely_benign	0.1803	benign	-0.96	Destabilizing	0.991	D	0.651	neutral	None	None	None	None	N
V/N	0.768	likely_pathogenic	0.7137	pathogenic	-1.721	Destabilizing	0.999	D	0.763	deleterious	None	None	None	None	N
V/P	0.9931	likely_pathogenic	0.9864	pathogenic	-1.227	Destabilizing	0.995	D	0.7	prob.neutral	None	None	None	None	N
V/Q	0.49	ambiguous	0.4314	ambiguous	-1.747	Destabilizing	0.999	D	0.715	prob.delet.	None	None	None	None	N
V/R	0.5168	ambiguous	0.4331	ambiguous	-1.231	Destabilizing	0.995	D	0.752	deleterious	None	None	None	None	N
V/S	0.5799	likely_pathogenic	0.5112	ambiguous	-2.359	Highly Destabilizing	0.939	D	0.679	prob.neutral	None	None	None	None	N
V/T	0.3652	ambiguous	0.3235	benign	-2.106	Highly Destabilizing	0.969	D	0.595	neutral	None	None	None	None	N
V/W	0.8908	likely_pathogenic	0.8673	pathogenic	-1.661	Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	N
V/Y	0.7032	likely_pathogenic	0.6728	pathogenic	-1.347	Destabilizing	0.999	D	0.704	prob.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.