TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7567	22924;22925;22926	chr2:178721964;178721963;178721962	chr2:179586691;179586690;179586689
N2AB	7250	21973;21974;21975	chr2:178721964;178721963;178721962	chr2:179586691;179586690;179586689
N2A	6323	19192;19193;19194	chr2:178721964;178721963;178721962	chr2:179586691;179586690;179586689
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: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Ig-60
• Domain position: 53
• Structural Position: 131
• Q(SASA): 0.4472
• Predicted PPI site: I

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
G/A	rs764311341	0.066	0.002	N	0.085	0.222	0.0986583533028	gnomAD-4.0.0	6.84327E-07	None	None	None	None	I	None	0	0	None	3.82907E-05	0	None	0	0	0	0	0
G/E	rs764311341	None	0.023	N	0.189	0.258	0.251116650651	gnomAD-4.0.0	1.36865E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79924E-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
G/A	0.131	likely_benign	0.1595	benign	-0.162	Destabilizing	0.002	N	0.085	neutral	N	0.499252749	None	None	I
G/C	0.3694	ambiguous	0.3824	ambiguous	-0.639	Destabilizing	0.985	D	0.361	neutral	None	None	None	None	I
G/D	0.1424	likely_benign	0.1578	benign	-0.977	Destabilizing	0.003	N	0.146	neutral	None	None	None	None	I
G/E	0.1615	likely_benign	0.1672	benign	-1.155	Destabilizing	0.023	N	0.189	neutral	N	0.471103355	None	None	I
G/F	0.6693	likely_pathogenic	0.7347	pathogenic	-1.059	Destabilizing	0.944	D	0.389	neutral	None	None	None	None	I
G/H	0.3916	ambiguous	0.4477	ambiguous	-0.433	Destabilizing	0.944	D	0.349	neutral	None	None	None	None	I
G/I	0.4771	ambiguous	0.555	ambiguous	-0.407	Destabilizing	0.893	D	0.421	neutral	None	None	None	None	I
G/K	0.4073	ambiguous	0.4445	ambiguous	-0.772	Destabilizing	0.704	D	0.281	neutral	None	None	None	None	I
G/L	0.472	ambiguous	0.5578	ambiguous	-0.407	Destabilizing	0.704	D	0.341	neutral	None	None	None	None	I
G/M	0.5628	ambiguous	0.6291	pathogenic	-0.394	Destabilizing	0.995	D	0.357	neutral	None	None	None	None	I
G/N	0.1957	likely_benign	0.2257	benign	-0.3	Destabilizing	0.031	N	0.141	neutral	None	None	None	None	I
G/P	0.7977	likely_pathogenic	0.87	pathogenic	-0.296	Destabilizing	0.828	D	0.397	neutral	None	None	None	None	I
G/Q	0.263	likely_benign	0.2874	benign	-0.645	Destabilizing	0.704	D	0.377	neutral	None	None	None	None	I
G/R	0.2806	likely_benign	0.3091	benign	-0.263	Destabilizing	0.642	D	0.39	neutral	N	0.479858912	None	None	I
G/S	0.101	likely_benign	0.115	benign	-0.326	Destabilizing	0.031	N	0.114	neutral	None	None	None	None	I
G/T	0.2488	likely_benign	0.2991	benign	-0.46	Destabilizing	0.329	N	0.287	neutral	None	None	None	None	I
G/V	0.3228	likely_benign	0.3907	ambiguous	-0.296	Destabilizing	0.473	N	0.342	neutral	N	0.462687689	None	None	I
G/W	0.4972	ambiguous	0.5225	ambiguous	-1.206	Destabilizing	0.995	D	0.379	neutral	None	None	None	None	I
G/Y	0.4975	ambiguous	0.5346	ambiguous	-0.867	Destabilizing	0.981	D	0.388	neutral	None	None	None	None	I

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.