TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1102	3529;3530;3531	chr2:178782288;178782287;178782286	chr2:179647015;179647014;179647013
N2AB	1102	3529;3530;3531	chr2:178782288;178782287;178782286	chr2:179647015;179647014;179647013
N2A	1102	3529;3530;3531	chr2:178782288;178782287;178782286	chr2:179647015;179647014;179647013
N2B	1056	3391;3392;3393	chr2:178782288;178782287;178782286	chr2:179647015;179647014;179647013
Novex-1	1056	3391;3392;3393	chr2:178782288;178782287;178782286	chr2:179647015;179647014;179647013
Novex-2	1056	3391;3392;3393	chr2:178782288;178782287;178782286	chr2:179647015;179647014;179647013
Novex-3	1102	3529;3530;3531	chr2:178782288;178782287;178782286	chr2:179647015;179647014;179647013

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Ig-4
• Domain position: 21
• Structural Position: 31
• Q(SASA): 0.2418
• 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/R	rs1016142990	None	0.017	N	0.46	0.161	0.62384306378	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
G/R	rs1016142990	None	0.017	N	0.46	0.161	0.62384306378	gnomAD-4.0.0	5.12184E-06	None	None	None	None	I	None	1.68776E-05	5.08233E-05	None	0	0	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
G/A	0.0685	likely_benign	0.0702	benign	-0.663	Destabilizing	0.003	N	0.327	neutral	N	0.397367865	None	None	I
G/C	0.1819	likely_benign	0.1802	benign	-0.806	Destabilizing	0.55	D	0.495	neutral	None	None	None	None	I
G/D	0.1436	likely_benign	0.1541	benign	-1.553	Destabilizing	None	N	0.247	neutral	None	None	None	None	I
G/E	0.0694	likely_benign	0.0714	benign	-1.515	Destabilizing	None	N	0.289	neutral	N	0.289434122	None	None	I
G/F	0.3861	ambiguous	0.3987	ambiguous	-0.817	Destabilizing	0.138	N	0.573	neutral	None	None	None	None	I
G/H	0.2184	likely_benign	0.2271	benign	-1.693	Destabilizing	None	N	0.355	neutral	None	None	None	None	I
G/I	0.0994	likely_benign	0.0986	benign	0.065	Stabilizing	0.003	N	0.411	neutral	None	None	None	None	I
G/K	0.2344	likely_benign	0.2331	benign	-1.233	Destabilizing	0.009	N	0.424	neutral	None	None	None	None	I
G/L	0.1666	likely_benign	0.166	benign	0.065	Stabilizing	0.009	N	0.429	neutral	None	None	None	None	I
G/M	0.2188	likely_benign	0.2235	benign	0.037	Stabilizing	0.138	N	0.505	neutral	None	None	None	None	I
G/N	0.1765	likely_benign	0.1851	benign	-1.042	Destabilizing	0.009	N	0.324	neutral	None	None	None	None	I
G/P	0.7275	likely_pathogenic	0.7431	pathogenic	-0.133	Destabilizing	0.085	N	0.475	neutral	None	None	None	None	I
G/Q	0.129	likely_benign	0.1347	benign	-1.069	Destabilizing	0.022	N	0.429	neutral	None	None	None	None	I
G/R	0.1766	likely_benign	0.18	benign	-1.147	Destabilizing	0.017	N	0.46	neutral	N	0.297969803	None	None	I
G/S	0.0711	likely_benign	0.0755	benign	-1.32	Destabilizing	0.009	N	0.335	neutral	None	None	None	None	I
G/T	0.072	likely_benign	0.0742	benign	-1.189	Destabilizing	0.018	N	0.399	neutral	None	None	None	None	I
G/V	0.0693	likely_benign	0.0707	benign	-0.133	Destabilizing	None	N	0.431	neutral	N	0.381210143	None	None	I
G/W	0.3239	likely_benign	0.3249	benign	-1.437	Destabilizing	0.788	D	0.513	neutral	None	None	None	None	I
G/Y	0.312	likely_benign	0.3218	benign	-0.904	Destabilizing	0.044	N	0.529	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.