TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7655	23188;23189;23190	chr2:178721056;178721055;178721054	chr2:179585783;179585782;179585781
N2AB	7338	22237;22238;22239	chr2:178721056;178721055;178721054	chr2:179585783;179585782;179585781
N2A	6411	19456;19457;19458	chr2:178721056;178721055;178721054	chr2:179585783;179585782;179585781
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: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-61
• Domain position: 48
• Structural Position: 121
• Q(SASA): 0.1556
• 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
Y/F	rs775036090	-1.06	0.801	N	0.51	0.206	0.505765104075	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
Y/F	rs775036090	-1.06	0.801	N	0.51	0.206	0.505765104075	gnomAD-4.0.0	1.59245E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86118E-06	0	0
Y/N	None	None	0.934	N	0.559	0.553	0.701728203507	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
Y/A	0.792	likely_pathogenic	0.8559	pathogenic	-3.049	Highly Destabilizing	0.842	D	0.505	neutral	None	None	None	None	N
Y/C	0.2819	likely_benign	0.3263	benign	-2.133	Highly Destabilizing	0.997	D	0.562	neutral	N	0.499952832	None	None	N
Y/D	0.7242	likely_pathogenic	0.8409	pathogenic	-3.332	Highly Destabilizing	0.966	D	0.623	neutral	N	0.514778631	None	None	N
Y/E	0.8625	likely_pathogenic	0.9227	pathogenic	-3.148	Highly Destabilizing	0.949	D	0.55	neutral	None	None	None	None	N
Y/F	0.1452	likely_benign	0.1693	benign	-1.152	Destabilizing	0.801	D	0.51	neutral	N	0.48828726	None	None	N
Y/G	0.7243	likely_pathogenic	0.7999	pathogenic	-3.472	Highly Destabilizing	0.974	D	0.586	neutral	None	None	None	None	N
Y/H	0.3703	ambiguous	0.4736	ambiguous	-2.12	Highly Destabilizing	0.028	N	0.375	neutral	N	0.495426663	None	None	N
Y/I	0.5598	ambiguous	0.6356	pathogenic	-1.662	Destabilizing	0.728	D	0.481	neutral	None	None	None	None	N
Y/K	0.8485	likely_pathogenic	0.909	pathogenic	-2.256	Highly Destabilizing	0.974	D	0.552	neutral	None	None	None	None	N
Y/L	0.5513	ambiguous	0.6112	pathogenic	-1.662	Destabilizing	0.016	N	0.321	neutral	None	None	None	None	N
Y/M	0.7025	likely_pathogenic	0.7683	pathogenic	-1.502	Destabilizing	0.949	D	0.562	neutral	None	None	None	None	N
Y/N	0.3706	ambiguous	0.4935	ambiguous	-2.999	Highly Destabilizing	0.934	D	0.559	neutral	N	0.508929281	None	None	N
Y/P	0.9817	likely_pathogenic	0.9873	pathogenic	-2.137	Highly Destabilizing	0.991	D	0.646	neutral	None	None	None	None	N
Y/Q	0.7719	likely_pathogenic	0.8655	pathogenic	-2.771	Highly Destabilizing	0.974	D	0.577	neutral	None	None	None	None	N
Y/R	0.7377	likely_pathogenic	0.8313	pathogenic	-1.948	Destabilizing	0.974	D	0.581	neutral	None	None	None	None	N
Y/S	0.5703	likely_pathogenic	0.696	pathogenic	-3.392	Highly Destabilizing	0.966	D	0.545	neutral	N	0.496812507	None	None	N
Y/T	0.6625	likely_pathogenic	0.769	pathogenic	-3.083	Highly Destabilizing	0.842	D	0.541	neutral	None	None	None	None	N
Y/V	0.4477	ambiguous	0.5197	ambiguous	-2.137	Highly Destabilizing	0.067	N	0.351	neutral	None	None	None	None	N
Y/W	0.5504	ambiguous	0.606	pathogenic	-0.594	Destabilizing	0.998	D	0.522	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.