TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7524	22795;22796;22797	chr2:178722093;178722092;178722091	chr2:179586820;179586819;179586818
N2AB	7207	21844;21845;21846	chr2:178722093;178722092;178722091	chr2:179586820;179586819;179586818
N2A	6280	19063;19064;19065	chr2:178722093;178722092;178722091	chr2:179586820;179586819;179586818
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: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Ig-60
• Domain position: 10
• Structural Position: 13
• Q(SASA): 0.3458
• 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
I/T	None	None	0.642	N	0.364	0.315	0.669942640896	gnomAD-4.0.0	1.61251E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.47063E-05	0
I/V	None	None	0.01	N	0.117	0.187	0.42805410278	gnomAD-4.0.0	3.22771E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.89729E-06	1.47336E-05	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
I/A	0.1297	likely_benign	0.1456	benign	-1.483	Destabilizing	0.495	N	0.371	neutral	None	None	None	None	N
I/C	0.6595	likely_pathogenic	0.6916	pathogenic	-0.967	Destabilizing	0.995	D	0.365	neutral	None	None	None	None	N
I/D	0.593	likely_pathogenic	0.6595	pathogenic	-0.432	Destabilizing	0.704	D	0.461	neutral	None	None	None	None	N
I/E	0.3595	ambiguous	0.4092	ambiguous	-0.383	Destabilizing	0.329	N	0.392	neutral	None	None	None	None	N
I/F	0.1422	likely_benign	0.1707	benign	-0.887	Destabilizing	0.944	D	0.399	neutral	None	None	None	None	N
I/G	0.4261	ambiguous	0.4892	ambiguous	-1.846	Destabilizing	0.704	D	0.432	neutral	None	None	None	None	N
I/H	0.4145	ambiguous	0.486	ambiguous	-1.036	Destabilizing	0.944	D	0.409	neutral	None	None	None	None	N
I/K	0.1967	likely_benign	0.2279	benign	-0.852	Destabilizing	0.006	N	0.393	neutral	N	0.516975371	None	None	N
I/L	0.094	likely_benign	0.1054	benign	-0.553	Destabilizing	0.139	N	0.235	neutral	N	0.474952603	None	None	N
I/M	0.0679	likely_benign	0.076	benign	-0.548	Destabilizing	0.927	D	0.412	neutral	D	0.529019161	None	None	N
I/N	0.2795	likely_benign	0.3242	benign	-0.749	Destabilizing	0.893	D	0.483	neutral	None	None	None	None	N
I/P	0.6759	likely_pathogenic	0.7401	pathogenic	-0.831	Destabilizing	0.944	D	0.483	neutral	None	None	None	None	N
I/Q	0.2552	likely_benign	0.3046	benign	-0.81	Destabilizing	0.037	N	0.361	neutral	None	None	None	None	N
I/R	0.1478	likely_benign	0.1797	benign	-0.44	Destabilizing	0.473	N	0.461	neutral	N	0.510049399	None	None	N
I/S	0.1958	likely_benign	0.2301	benign	-1.475	Destabilizing	0.704	D	0.358	neutral	None	None	None	None	N
I/T	0.08	likely_benign	0.0883	benign	-1.291	Destabilizing	0.642	D	0.364	neutral	N	0.482785439	None	None	N
I/V	0.0626	likely_benign	0.0645	benign	-0.831	Destabilizing	0.01	N	0.117	neutral	N	0.44920601	None	None	N
I/W	0.6532	likely_pathogenic	0.7254	pathogenic	-0.972	Destabilizing	0.995	D	0.453	neutral	None	None	None	None	N
I/Y	0.5039	ambiguous	0.5594	ambiguous	-0.717	Destabilizing	0.981	D	0.452	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.