TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6415	19468;19469;19470	chr2:178728683;178728682;178728681	chr2:179593410;179593409;179593408
N2AB	6098	18517;18518;18519	chr2:178728683;178728682;178728681	chr2:179593410;179593409;179593408
N2A	5171	15736;15737;15738	chr2:178728683;178728682;178728681	chr2:179593410;179593409;179593408
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-48
• Domain position: 31
• Structural Position: 45
• Q(SASA): 0.6559
• 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	rs1236523365	0.447	0.042	N	0.383	0.15	0.223847106136	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	2.91E-05	None	0	0	None	0	None	0	0	0
K/E	rs1236523365	0.447	0.042	N	0.383	0.15	0.223847106136	gnomAD-4.0.0	1.59233E-06	None	None	None	None	N	None	0	2.28948E-05	None	0	0	None	0	0	0	0	0
K/N	None	None	0.175	N	0.373	0.181	0.227260227426	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/R	rs775494513	-0.01	None	N	0.13	0.111	0.21279746466	gnomAD-2.1.1	8.06E-06	None	None	None	None	N	None	0	2.91E-05	None	0	0	None	0	None	0	8.91E-06	0
K/R	rs775494513	-0.01	None	N	0.13	0.111	0.21279746466	gnomAD-4.0.0	2.73757E-06	None	None	None	None	N	None	0	2.23884E-05	None	0	0	None	0	0	2.69883E-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
K/A	0.3321	likely_benign	0.3335	benign	-0.196	Destabilizing	0.055	N	0.391	neutral	None	None	None	None	N
K/C	0.684	likely_pathogenic	0.7057	pathogenic	-0.316	Destabilizing	0.958	D	0.467	neutral	None	None	None	None	N
K/D	0.5833	likely_pathogenic	0.5439	ambiguous	0.05	Stabilizing	0.22	N	0.474	neutral	None	None	None	None	N
K/E	0.1949	likely_benign	0.188	benign	0.121	Stabilizing	0.042	N	0.383	neutral	N	0.501368413	None	None	N
K/F	0.7559	likely_pathogenic	0.7583	pathogenic	0.017	Stabilizing	0.497	N	0.489	neutral	None	None	None	None	N
K/G	0.4924	ambiguous	0.4801	ambiguous	-0.51	Destabilizing	0.22	N	0.49	neutral	None	None	None	None	N
K/H	0.2143	likely_benign	0.2049	benign	-0.788	Destabilizing	0.497	N	0.484	neutral	None	None	None	None	N
K/I	0.3561	ambiguous	0.3684	ambiguous	0.587	Stabilizing	0.002	N	0.357	neutral	N	0.496874959	None	None	N
K/L	0.3298	likely_benign	0.3416	ambiguous	0.587	Stabilizing	0.02	N	0.399	neutral	None	None	None	None	N
K/M	0.2404	likely_benign	0.2571	benign	0.29	Stabilizing	0.497	N	0.483	neutral	None	None	None	None	N
K/N	0.3279	likely_benign	0.3202	benign	-0.091	Destabilizing	0.175	N	0.373	neutral	N	0.518975526	None	None	N
K/P	0.8725	likely_pathogenic	0.8511	pathogenic	0.357	Stabilizing	0.667	D	0.537	neutral	None	None	None	None	N
K/Q	0.1027	likely_benign	0.1002	benign	-0.181	Destabilizing	0.003	N	0.149	neutral	N	0.473491166	None	None	N
K/R	0.078	likely_benign	0.0748	benign	-0.369	Destabilizing	None	N	0.13	neutral	N	0.521765115	None	None	N
K/S	0.3579	ambiguous	0.3516	ambiguous	-0.643	Destabilizing	0.055	N	0.366	neutral	None	None	None	None	N
K/T	0.1514	likely_benign	0.1576	benign	-0.389	Destabilizing	0.001	N	0.214	neutral	N	0.441610821	None	None	N
K/V	0.3217	likely_benign	0.336	benign	0.357	Stabilizing	0.02	N	0.423	neutral	None	None	None	None	N
K/W	0.6792	likely_pathogenic	0.6709	pathogenic	0.082	Stabilizing	0.958	D	0.482	neutral	None	None	None	None	N
K/Y	0.5967	likely_pathogenic	0.6054	pathogenic	0.369	Stabilizing	0.667	D	0.487	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.