TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7753	23482;23483;23484	chr2:178720505;178720504;178720503	chr2:179585232;179585231;179585230
N2AB	7436	22531;22532;22533	chr2:178720505;178720504;178720503	chr2:179585232;179585231;179585230
N2A	6509	19750;19751;19752	chr2:178720505;178720504;178720503	chr2:179585232;179585231;179585230
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: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-62
• Domain position: 52
• Structural Position: 130
• Q(SASA): 0.6779
• 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
K/E	None	None	0.959	N	0.311	0.269	0.30212335484	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
K/N	None	None	0.994	N	0.321	0.239	0.287603790349	gnomAD-4.0.0	6.84279E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99549E-07	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
K/A	0.3861	ambiguous	0.4362	ambiguous	-0.004	Destabilizing	0.963	D	0.347	neutral	None	None	None	None	N
K/C	0.7609	likely_pathogenic	0.8011	pathogenic	0.041	Stabilizing	1.0	D	0.312	neutral	None	None	None	None	N
K/D	0.5506	ambiguous	0.5975	pathogenic	0.002	Stabilizing	0.995	D	0.355	neutral	None	None	None	None	N
K/E	0.1918	likely_benign	0.2217	benign	None	Stabilizing	0.959	D	0.311	neutral	N	0.430873752	None	None	N
K/F	0.8117	likely_pathogenic	0.8467	pathogenic	-0.267	Destabilizing	0.991	D	0.341	neutral	None	None	None	None	N
K/G	0.4569	ambiguous	0.5152	ambiguous	-0.203	Destabilizing	0.984	D	0.36	neutral	None	None	None	None	N
K/H	0.3184	likely_benign	0.3519	ambiguous	-0.626	Destabilizing	1.0	D	0.33	neutral	None	None	None	None	N
K/I	0.4277	ambiguous	0.4616	ambiguous	0.441	Stabilizing	0.238	N	0.305	neutral	D	0.524864135	None	None	N
K/L	0.4164	ambiguous	0.4602	ambiguous	0.441	Stabilizing	0.088	N	0.217	neutral	None	None	None	None	N
K/M	0.3196	likely_benign	0.3522	ambiguous	0.373	Stabilizing	0.991	D	0.327	neutral	None	None	None	None	N
K/N	0.3988	ambiguous	0.4441	ambiguous	0.412	Stabilizing	0.994	D	0.321	neutral	N	0.495829308	None	None	N
K/P	0.8259	likely_pathogenic	0.8629	pathogenic	0.32	Stabilizing	0.999	D	0.343	neutral	None	None	None	None	N
K/Q	0.1266	likely_benign	0.1389	benign	0.202	Stabilizing	0.988	D	0.349	neutral	N	0.488980693	None	None	N
K/R	0.0827	likely_benign	0.0866	benign	0.022	Stabilizing	0.068	N	0.168	neutral	N	0.498504253	None	None	N
K/S	0.3839	ambiguous	0.4263	ambiguous	-0.045	Destabilizing	0.984	D	0.294	neutral	None	None	None	None	N
K/T	0.2	likely_benign	0.2229	benign	0.098	Stabilizing	0.979	D	0.324	neutral	N	0.477974266	None	None	N
K/V	0.3792	ambiguous	0.415	ambiguous	0.32	Stabilizing	0.864	D	0.35	neutral	None	None	None	None	N
K/W	0.8177	likely_pathogenic	0.8508	pathogenic	-0.285	Destabilizing	1.0	D	0.393	neutral	None	None	None	None	N
K/Y	0.6973	likely_pathogenic	0.7402	pathogenic	0.077	Stabilizing	0.999	D	0.338	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.