TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6262	19009;19010;19011	chr2:178729372;178729371;178729370	chr2:179594099;179594098;179594097
N2AB	5945	18058;18059;18060	chr2:178729372;178729371;178729370	chr2:179594099;179594098;179594097
N2A	5018	15277;15278;15279	chr2:178729372;178729371;178729370	chr2:179594099;179594098;179594097
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: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-46
• Domain position: 64
• Structural Position: 145
• Q(SASA): 0.2654
• 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
D/G	rs757214692	-0.515	0.003	N	0.158	0.336	0.195762928549	gnomAD-2.1.1	1.61E-05	None	None	None	None	N	None	0	0	None	0	2.22792E-04	None	0	None	0	0	0
D/G	rs757214692	-0.515	0.003	N	0.158	0.336	0.195762928549	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	0	0	0	0	3.86698E-04	None	0	0	0	0	0
D/G	rs757214692	-0.515	0.003	N	0.158	0.336	0.195762928549	gnomAD-4.0.0	2.56301E-05	None	None	None	None	N	None	0	0	None	0	4.8506E-04	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
D/A	0.2446	likely_benign	0.2776	benign	-0.477	Destabilizing	0.007	N	0.233	neutral	N	0.514356353	None	None	N
D/C	0.7374	likely_pathogenic	0.78	pathogenic	-0.128	Destabilizing	0.987	D	0.447	neutral	None	None	None	None	N
D/E	0.1434	likely_benign	0.1632	benign	-0.762	Destabilizing	0.007	N	0.193	neutral	N	0.440973315	None	None	N
D/F	0.5447	ambiguous	0.599	pathogenic	-0.32	Destabilizing	0.953	D	0.449	neutral	None	None	None	None	N
D/G	0.2837	likely_benign	0.308	benign	-0.804	Destabilizing	0.003	N	0.158	neutral	N	0.473741882	None	None	N
D/H	0.3525	ambiguous	0.3964	ambiguous	-0.709	Destabilizing	0.939	D	0.362	neutral	D	0.528499086	None	None	N
D/I	0.358	ambiguous	0.4171	ambiguous	0.375	Stabilizing	0.91	D	0.459	neutral	None	None	None	None	N
D/K	0.5059	ambiguous	0.5462	ambiguous	-0.437	Destabilizing	0.59	D	0.317	neutral	None	None	None	None	N
D/L	0.354	ambiguous	0.4018	ambiguous	0.375	Stabilizing	0.59	D	0.431	neutral	None	None	None	None	N
D/M	0.5907	likely_pathogenic	0.6473	pathogenic	0.896	Stabilizing	0.996	D	0.434	neutral	None	None	None	None	N
D/N	0.1341	likely_benign	0.1465	benign	-0.825	Destabilizing	0.028	N	0.249	neutral	N	0.486612391	None	None	N
D/P	0.8998	likely_pathogenic	0.9007	pathogenic	0.117	Stabilizing	0.953	D	0.359	neutral	None	None	None	None	N
D/Q	0.3913	ambiguous	0.4332	ambiguous	-0.67	Destabilizing	0.835	D	0.341	neutral	None	None	None	None	N
D/R	0.5545	ambiguous	0.6033	pathogenic	-0.346	Destabilizing	0.91	D	0.414	neutral	None	None	None	None	N
D/S	0.1579	likely_benign	0.1724	benign	-1.018	Destabilizing	0.373	N	0.318	neutral	None	None	None	None	N
D/T	0.3064	likely_benign	0.3502	ambiguous	-0.753	Destabilizing	0.742	D	0.314	neutral	None	None	None	None	N
D/V	0.2624	likely_benign	0.307	benign	0.117	Stabilizing	0.521	D	0.415	neutral	N	0.458196426	None	None	N
D/W	0.913	likely_pathogenic	0.9286	pathogenic	-0.238	Destabilizing	0.996	D	0.561	neutral	None	None	None	None	N
D/Y	0.2857	likely_benign	0.3157	benign	-0.128	Destabilizing	0.979	D	0.447	neutral	N	0.486150537	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.