TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25563	76912;76913;76914	chr2:178569445;178569444;178569443	chr2:179434172;179434171;179434170
N2AB	23922	71989;71990;71991	chr2:178569445;178569444;178569443	chr2:179434172;179434171;179434170
N2A	22995	69208;69209;69210	chr2:178569445;178569444;178569443	chr2:179434172;179434171;179434170
N2B	16498	49717;49718;49719	chr2:178569445;178569444;178569443	chr2:179434172;179434171;179434170
Novex-1	16623	50092;50093;50094	chr2:178569445;178569444;178569443	chr2:179434172;179434171;179434170
Novex-2	16690	50293;50294;50295	chr2:178569445;178569444;178569443	chr2:179434172;179434171;179434170
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTC
• RefSeq wild type template codon: AAG
• Domain: Ig-135
• Domain position: 50
• Structural Position: 135
• Q(SASA): 0.1836
• 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
F/Y	rs1273963065	-0.242	0.219	N	0.178	0.188	0.404453528171	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
F/Y	rs1273963065	-0.242	0.219	N	0.178	0.188	0.404453528171	gnomAD-4.0.0	4.77775E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.58079E-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
F/A	0.8747	likely_pathogenic	0.8589	pathogenic	-2.229	Highly Destabilizing	0.993	D	0.511	neutral	None	None	None	None	N
F/C	0.4922	ambiguous	0.4509	ambiguous	-1.341	Destabilizing	1.0	D	0.651	neutral	N	0.513721635	None	None	N
F/D	0.9697	likely_pathogenic	0.9637	pathogenic	-0.956	Destabilizing	0.999	D	0.671	neutral	None	None	None	None	N
F/E	0.9768	likely_pathogenic	0.972	pathogenic	-0.836	Destabilizing	0.999	D	0.655	neutral	None	None	None	None	N
F/G	0.9418	likely_pathogenic	0.9367	pathogenic	-2.59	Highly Destabilizing	0.999	D	0.599	neutral	None	None	None	None	N
F/H	0.7152	likely_pathogenic	0.664	pathogenic	-0.96	Destabilizing	0.996	D	0.575	neutral	None	None	None	None	N
F/I	0.6741	likely_pathogenic	0.6279	pathogenic	-1.126	Destabilizing	0.99	D	0.43	neutral	N	0.474587244	None	None	N
F/K	0.9693	likely_pathogenic	0.965	pathogenic	-1.105	Destabilizing	0.998	D	0.657	neutral	None	None	None	None	N
F/L	0.9665	likely_pathogenic	0.96	pathogenic	-1.126	Destabilizing	0.953	D	0.459	neutral	N	0.470104144	None	None	N
F/M	0.7975	likely_pathogenic	0.7803	pathogenic	-0.939	Destabilizing	0.999	D	0.492	neutral	None	None	None	None	N
F/N	0.8772	likely_pathogenic	0.8528	pathogenic	-1.169	Destabilizing	0.999	D	0.671	neutral	None	None	None	None	N
F/P	0.9992	likely_pathogenic	0.9991	pathogenic	-1.49	Destabilizing	0.999	D	0.676	prob.neutral	None	None	None	None	N
F/Q	0.9337	likely_pathogenic	0.9242	pathogenic	-1.227	Destabilizing	0.999	D	0.674	neutral	None	None	None	None	N
F/R	0.9239	likely_pathogenic	0.918	pathogenic	-0.546	Destabilizing	0.998	D	0.67	neutral	None	None	None	None	N
F/S	0.7065	likely_pathogenic	0.6744	pathogenic	-2.062	Highly Destabilizing	0.997	D	0.581	neutral	N	0.435490138	None	None	N
F/T	0.8619	likely_pathogenic	0.8312	pathogenic	-1.845	Destabilizing	0.998	D	0.585	neutral	None	None	None	None	N
F/V	0.5835	likely_pathogenic	0.5428	ambiguous	-1.49	Destabilizing	0.98	D	0.44	neutral	N	0.477646192	None	None	N
F/W	0.6175	likely_pathogenic	0.6175	pathogenic	-0.303	Destabilizing	0.999	D	0.499	neutral	None	None	None	None	N
F/Y	0.1028	likely_benign	0.1044	benign	-0.499	Destabilizing	0.219	N	0.178	neutral	N	0.408498325	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.