TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24130	72613;72614;72615	chr2:178573744;178573743;178573742	chr2:179438471;179438470;179438469
N2AB	22489	67690;67691;67692	chr2:178573744;178573743;178573742	chr2:179438471;179438470;179438469
N2A	21562	64909;64910;64911	chr2:178573744;178573743;178573742	chr2:179438471;179438470;179438469
N2B	15065	45418;45419;45420	chr2:178573744;178573743;178573742	chr2:179438471;179438470;179438469
Novex-1	15190	45793;45794;45795	chr2:178573744;178573743;178573742	chr2:179438471;179438470;179438469
Novex-2	15257	45994;45995;45996	chr2:178573744;178573743;178573742	chr2:179438471;179438470;179438469
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Fn3-63
• Domain position: 9
• Structural Position: 9
• Q(SASA): 0.1457
• 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
L/F	rs376664950	-1.657	0.997	N	0.844	0.34	0.306695030598	gnomAD-2.1.1	4.62E-06	None	None	None	None	N	None	0	3.44E-05	None	0	0	None	0	None	0	0	0
L/F	rs376664950	-1.657	0.997	N	0.844	0.34	0.306695030598	gnomAD-4.0.0	1.40585E-06	None	None	None	None	N	None	0	5.18968E-05	None	0	0	None	0	0	0	0	0
L/S	None	None	0.997	D	0.819	0.552	0.848911306636	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

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
L/A	0.7481	likely_pathogenic	0.8132	pathogenic	-2.102	Highly Destabilizing	0.966	D	0.675	neutral	None	None	None	None	N
L/C	0.8228	likely_pathogenic	0.8699	pathogenic	-1.536	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
L/D	0.9981	likely_pathogenic	0.9984	pathogenic	-1.909	Destabilizing	0.999	D	0.88	deleterious	None	None	None	None	N
L/E	0.9879	likely_pathogenic	0.9881	pathogenic	-1.698	Destabilizing	0.998	D	0.857	deleterious	None	None	None	None	N
L/F	0.4543	ambiguous	0.622	pathogenic	-1.165	Destabilizing	0.997	D	0.844	deleterious	N	0.508730881	None	None	N
L/G	0.9719	likely_pathogenic	0.9807	pathogenic	-2.634	Highly Destabilizing	0.998	D	0.841	deleterious	None	None	None	None	N
L/H	0.9774	likely_pathogenic	0.9837	pathogenic	-2.127	Highly Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
L/I	0.1087	likely_benign	0.1277	benign	-0.589	Destabilizing	0.921	D	0.677	prob.neutral	None	None	None	None	N
L/K	0.9849	likely_pathogenic	0.9839	pathogenic	-1.432	Destabilizing	0.998	D	0.819	deleterious	None	None	None	None	N
L/M	0.1953	likely_benign	0.2535	benign	-0.709	Destabilizing	0.997	D	0.798	deleterious	N	0.509744839	None	None	N
L/N	0.9884	likely_pathogenic	0.9898	pathogenic	-1.676	Destabilizing	0.999	D	0.887	deleterious	None	None	None	None	N
L/P	0.8787	likely_pathogenic	0.8882	pathogenic	-1.07	Destabilizing	0.999	D	0.871	deleterious	None	None	None	None	N
L/Q	0.963	likely_pathogenic	0.9687	pathogenic	-1.53	Destabilizing	0.999	D	0.867	deleterious	None	None	None	None	N
L/R	0.9711	likely_pathogenic	0.9722	pathogenic	-1.291	Destabilizing	0.998	D	0.852	deleterious	None	None	None	None	N
L/S	0.9574	likely_pathogenic	0.9718	pathogenic	-2.436	Highly Destabilizing	0.997	D	0.819	deleterious	D	0.546295744	None	None	N
L/T	0.82	likely_pathogenic	0.8707	pathogenic	-2.072	Highly Destabilizing	0.995	D	0.783	deleterious	None	None	None	None	N
L/V	0.1067	likely_benign	0.1353	benign	-1.07	Destabilizing	0.117	N	0.333	neutral	N	0.456667913	None	None	N
L/W	0.9322	likely_pathogenic	0.9571	pathogenic	-1.483	Destabilizing	1.0	D	0.806	deleterious	D	0.546802723	None	None	N
L/Y	0.9441	likely_pathogenic	0.9646	pathogenic	-1.156	Destabilizing	0.999	D	0.803	deleterious	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.