TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22910	68953;68954;68955	chr2:178577698;178577697;178577696	chr2:179442425;179442424;179442423
N2AB	21269	64030;64031;64032	chr2:178577698;178577697;178577696	chr2:179442425;179442424;179442423
N2A	20342	61249;61250;61251	chr2:178577698;178577697;178577696	chr2:179442425;179442424;179442423
N2B	13845	41758;41759;41760	chr2:178577698;178577697;178577696	chr2:179442425;179442424;179442423
Novex-1	13970	42133;42134;42135	chr2:178577698;178577697;178577696	chr2:179442425;179442424;179442423
Novex-2	14037	42334;42335;42336	chr2:178577698;178577697;178577696	chr2:179442425;179442424;179442423
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Fn3-54
• Domain position: 70
• Structural Position: 102
• Q(SASA): 0.1893
• 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
G/R	rs794729245	None	0.792	N	0.469	0.222	0.415055319159	gnomAD-4.0.0	6.8442E-07	None	None	None	None	N	None	2.989E-05	0	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	0.1041	likely_benign	0.1099	benign	-0.518	Destabilizing	0.164	N	0.311	neutral	N	0.378988202	None	None	N
G/C	0.1406	likely_benign	0.1534	benign	-0.772	Destabilizing	0.009	N	0.286	neutral	None	None	None	None	N
G/D	0.2437	likely_benign	0.2782	benign	-0.88	Destabilizing	0.742	D	0.439	neutral	None	None	None	None	N
G/E	0.2051	likely_benign	0.2329	benign	-0.899	Destabilizing	0.521	D	0.426	neutral	N	0.37169687	None	None	N
G/F	0.5387	ambiguous	0.5931	pathogenic	-0.742	Destabilizing	0.984	D	0.537	neutral	None	None	None	None	N
G/H	0.3582	ambiguous	0.3859	ambiguous	-1.153	Destabilizing	0.987	D	0.476	neutral	None	None	None	None	N
G/I	0.295	likely_benign	0.355	ambiguous	-0.042	Destabilizing	0.91	D	0.517	neutral	None	None	None	None	N
G/K	0.3634	ambiguous	0.4033	ambiguous	-1.128	Destabilizing	0.009	N	0.271	neutral	None	None	None	None	N
G/L	0.3536	ambiguous	0.3966	ambiguous	-0.042	Destabilizing	0.59	D	0.468	neutral	None	None	None	None	N
G/M	0.3614	ambiguous	0.4043	ambiguous	-0.126	Destabilizing	0.984	D	0.517	neutral	None	None	None	None	N
G/N	0.2363	likely_benign	0.261	benign	-0.899	Destabilizing	0.742	D	0.457	neutral	None	None	None	None	N
G/P	0.963	likely_pathogenic	0.972	pathogenic	-0.158	Destabilizing	0.953	D	0.488	neutral	None	None	None	None	N
G/Q	0.2446	likely_benign	0.2626	benign	-0.991	Destabilizing	0.91	D	0.495	neutral	None	None	None	None	N
G/R	0.2841	likely_benign	0.3067	benign	-0.885	Destabilizing	0.792	D	0.469	neutral	N	0.388434405	None	None	N
G/S	0.087	likely_benign	0.0879	benign	-1.193	Destabilizing	0.016	N	0.099	neutral	None	None	None	None	N
G/T	0.1474	likely_benign	0.1685	benign	-1.117	Destabilizing	0.59	D	0.389	neutral	None	None	None	None	N
G/V	0.2068	likely_benign	0.2474	benign	-0.158	Destabilizing	0.684	D	0.501	neutral	N	0.397632678	None	None	N
G/W	0.4548	ambiguous	0.4989	ambiguous	-1.191	Destabilizing	0.996	D	0.484	neutral	None	None	None	None	N
G/Y	0.3956	ambiguous	0.4432	ambiguous	-0.71	Destabilizing	0.984	D	0.53	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.