TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6720	20383;20384;20385	chr2:178727207;178727206;178727205	chr2:179591934;179591933;179591932
N2AB	6403	19432;19433;19434	chr2:178727207;178727206;178727205	chr2:179591934;179591933;179591932
N2A	5476	16651;16652;16653	chr2:178727207;178727206;178727205	chr2:179591934;179591933;179591932
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: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-51
• Domain position: 54
• Structural Position: 131
• Q(SASA): 0.8226
• 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
D/V	rs1181953856	0.333	0.991	N	0.572	0.449	0.440077040801	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
D/V	rs1181953856	0.333	0.991	N	0.572	0.449	0.440077040801	gnomAD-4.0.0	1.59247E-06	None	None	None	None	I	None	0	2.28854E-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
D/A	0.4016	ambiguous	0.418	ambiguous	-0.016	Destabilizing	0.939	D	0.415	neutral	N	0.458187329	None	None	I
D/C	0.8975	likely_pathogenic	0.9042	pathogenic	-0.279	Destabilizing	0.999	D	0.646	neutral	None	None	None	None	I
D/E	0.2717	likely_benign	0.2485	benign	-0.389	Destabilizing	0.046	N	0.287	neutral	N	0.482066924	None	None	I
D/F	0.9011	likely_pathogenic	0.9151	pathogenic	0.015	Stabilizing	0.999	D	0.577	neutral	None	None	None	None	I
D/G	0.2367	likely_benign	0.2542	benign	-0.138	Destabilizing	0.939	D	0.513	neutral	N	0.448431566	None	None	I
D/H	0.5002	ambiguous	0.5291	ambiguous	0.675	Stabilizing	0.998	D	0.529	neutral	N	0.492029209	None	None	I
D/I	0.8786	likely_pathogenic	0.8829	pathogenic	0.245	Stabilizing	0.998	D	0.591	neutral	None	None	None	None	I
D/K	0.6546	likely_pathogenic	0.6879	pathogenic	0.441	Stabilizing	0.91	D	0.477	neutral	None	None	None	None	I
D/L	0.7964	likely_pathogenic	0.8177	pathogenic	0.245	Stabilizing	0.993	D	0.571	neutral	None	None	None	None	I
D/M	0.9268	likely_pathogenic	0.9299	pathogenic	-0.016	Destabilizing	0.999	D	0.6	neutral	None	None	None	None	I
D/N	0.13	likely_benign	0.1383	benign	-0.017	Destabilizing	0.322	N	0.29	neutral	N	0.455208396	None	None	I
D/P	0.8839	likely_pathogenic	0.8606	pathogenic	0.177	Stabilizing	0.993	D	0.509	neutral	None	None	None	None	I
D/Q	0.5562	ambiguous	0.5638	ambiguous	0.015	Stabilizing	0.973	D	0.535	neutral	None	None	None	None	I
D/R	0.6509	likely_pathogenic	0.6829	pathogenic	0.717	Stabilizing	0.986	D	0.513	neutral	None	None	None	None	I
D/S	0.2094	likely_benign	0.2244	benign	-0.05	Destabilizing	0.953	D	0.469	neutral	None	None	None	None	I
D/T	0.6196	likely_pathogenic	0.6263	pathogenic	0.063	Stabilizing	0.986	D	0.467	neutral	None	None	None	None	I
D/V	0.7329	likely_pathogenic	0.7412	pathogenic	0.177	Stabilizing	0.991	D	0.572	neutral	N	0.481179883	None	None	I
D/W	0.9724	likely_pathogenic	0.9743	pathogenic	0.088	Stabilizing	0.999	D	0.664	neutral	None	None	None	None	I
D/Y	0.5108	ambiguous	0.5547	ambiguous	0.243	Stabilizing	0.999	D	0.575	neutral	N	0.471963171	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.