TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32489	97690;97691;97692	chr2:178542291;178542290;178542289	chr2:179407018;179407017;179407016
N2AB	30848	92767;92768;92769	chr2:178542291;178542290;178542289	chr2:179407018;179407017;179407016
N2A	29921	89986;89987;89988	chr2:178542291;178542290;178542289	chr2:179407018;179407017;179407016
N2B	23424	70495;70496;70497	chr2:178542291;178542290;178542289	chr2:179407018;179407017;179407016
Novex-1	23549	70870;70871;70872	chr2:178542291;178542290;178542289	chr2:179407018;179407017;179407016
Novex-2	23616	71071;71072;71073	chr2:178542291;178542290;178542289	chr2:179407018;179407017;179407016
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-124
• Domain position: 91
• Structural Position: 124
• Q(SASA): 0.2931
• 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
E/G	rs987967114	-1.253	0.988	N	0.609	0.268	0.311079019809	gnomAD-2.1.1	8.2E-06	None	None	None	None	N	None	0	5.87E-05	None	0	0	None	0	None	0	0	0
E/G	rs987967114	-1.253	0.988	N	0.609	0.268	0.311079019809	gnomAD-4.0.0	3.19546E-06	None	None	None	None	N	None	0	4.60172E-05	None	0	0	None	0	0	0	0	0
E/Q	None	None	0.787	N	0.439	0.246	0.128392430309	gnomAD-4.0.0	4.79278E-06	None	None	None	None	N	None	0	6.90131E-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
E/A	0.1514	likely_benign	0.1327	benign	-0.141	Destabilizing	0.976	D	0.569	neutral	N	0.507445371	None	None	N
E/C	0.8228	likely_pathogenic	0.7508	pathogenic	-0.283	Destabilizing	1.0	D	0.545	neutral	None	None	None	None	N
E/D	0.0699	likely_benign	0.0692	benign	-0.453	Destabilizing	0.976	D	0.607	neutral	N	0.452976168	None	None	N
E/F	0.8377	likely_pathogenic	0.7602	pathogenic	0.203	Stabilizing	1.0	D	0.592	neutral	None	None	None	None	N
E/G	0.154	likely_benign	0.144	benign	-0.351	Destabilizing	0.988	D	0.609	neutral	N	0.513160622	None	None	N
E/H	0.4301	ambiguous	0.3753	ambiguous	0.711	Stabilizing	0.999	D	0.515	neutral	None	None	None	None	N
E/I	0.5035	ambiguous	0.4129	ambiguous	0.384	Stabilizing	0.999	D	0.649	prob.neutral	None	None	None	None	N
E/K	0.1455	likely_benign	0.1293	benign	0.456	Stabilizing	0.954	D	0.587	neutral	N	0.495940298	None	None	N
E/L	0.5024	ambiguous	0.4193	ambiguous	0.384	Stabilizing	0.997	D	0.629	neutral	None	None	None	None	N
E/M	0.5591	ambiguous	0.4628	ambiguous	0.165	Stabilizing	1.0	D	0.528	neutral	None	None	None	None	N
E/N	0.1663	likely_benign	0.1442	benign	-0.213	Destabilizing	0.997	D	0.493	neutral	None	None	None	None	N
E/P	0.2699	likely_benign	0.2653	benign	0.229	Stabilizing	0.145	N	0.499	neutral	None	None	None	None	N
E/Q	0.1655	likely_benign	0.1465	benign	-0.117	Destabilizing	0.787	D	0.439	neutral	N	0.514872775	None	None	N
E/R	0.2612	likely_benign	0.2214	benign	0.803	Stabilizing	0.995	D	0.508	neutral	None	None	None	None	N
E/S	0.1585	likely_benign	0.1383	benign	-0.289	Destabilizing	0.982	D	0.555	neutral	None	None	None	None	N
E/T	0.2235	likely_benign	0.1859	benign	-0.094	Destabilizing	0.997	D	0.533	neutral	None	None	None	None	N
E/V	0.2963	likely_benign	0.2423	benign	0.229	Stabilizing	0.997	D	0.591	neutral	N	0.46489928	None	None	N
E/W	0.9175	likely_pathogenic	0.8671	pathogenic	0.379	Stabilizing	1.0	D	0.527	neutral	None	None	None	None	N
E/Y	0.6814	likely_pathogenic	0.5848	pathogenic	0.462	Stabilizing	0.999	D	0.596	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.