TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14149	42670;42671;42672	chr2:178634054;178634053;178634052	chr2:179498781;179498780;179498779
N2AB	12508	37747;37748;37749	chr2:178634054;178634053;178634052	chr2:179498781;179498780;179498779
N2A	11581	34966;34967;34968	chr2:178634054;178634053;178634052	chr2:179498781;179498780;179498779
N2B	5084	15475;15476;15477	chr2:178634054;178634053;178634052	chr2:179498781;179498780;179498779
Novex-1	5209	15850;15851;15852	chr2:178634054;178634053;178634052	chr2:179498781;179498780;179498779
Novex-2	5276	16051;16052;16053	chr2:178634054;178634053;178634052	chr2:179498781;179498780;179498779
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-92
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.72
• 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/K	None	None	0.002	N	0.129	0.233	0.247322355667	gnomAD-4.0.0	1.36901E-06	None	None	None	None	N	None	2.99133E-05	0	None	0	0	None	0	0	8.99722E-07	0	0
E/Q	None	None	0.01	N	0.135	0.097	0.286848849266	gnomAD-4.0.0	6.84507E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99722E-07	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	0.1043	likely_benign	0.1182	benign	-0.421	Destabilizing	0.139	N	0.213	neutral	N	0.475481044	None	None	N
E/C	0.7041	likely_pathogenic	0.7573	pathogenic	-0.263	Destabilizing	0.995	D	0.267	neutral	None	None	None	None	N
E/D	0.1588	likely_benign	0.1796	benign	-0.435	Destabilizing	0.425	N	0.221	neutral	N	0.502657247	None	None	N
E/F	0.6319	likely_pathogenic	0.6937	pathogenic	-0.115	Destabilizing	0.981	D	0.299	neutral	None	None	None	None	N
E/G	0.1307	likely_benign	0.1405	benign	-0.662	Destabilizing	0.002	N	0.19	neutral	N	0.50941196	None	None	N
E/H	0.2909	likely_benign	0.3442	ambiguous	0.071	Stabilizing	0.944	D	0.331	neutral	None	None	None	None	N
E/I	0.249	likely_benign	0.2806	benign	0.194	Stabilizing	0.893	D	0.365	neutral	None	None	None	None	N
E/K	0.0734	likely_benign	0.0743	benign	0.023	Stabilizing	0.002	N	0.129	neutral	N	0.378770873	None	None	N
E/L	0.2501	likely_benign	0.287	benign	0.194	Stabilizing	0.495	N	0.34	neutral	None	None	None	None	N
E/M	0.3164	likely_benign	0.3519	ambiguous	0.196	Stabilizing	0.944	D	0.289	neutral	None	None	None	None	N
E/N	0.2009	likely_benign	0.2184	benign	-0.309	Destabilizing	0.495	N	0.259	neutral	None	None	None	None	N
E/P	0.5366	ambiguous	0.6774	pathogenic	0.009	Stabilizing	0.828	D	0.325	neutral	None	None	None	None	N
E/Q	0.0845	likely_benign	0.0947	benign	-0.236	Destabilizing	0.01	N	0.135	neutral	N	0.402515489	None	None	N
E/R	0.1286	likely_benign	0.1466	benign	0.335	Stabilizing	0.329	N	0.259	neutral	None	None	None	None	N
E/S	0.1428	likely_benign	0.1591	benign	-0.505	Destabilizing	0.037	N	0.169	neutral	None	None	None	None	N
E/T	0.1379	likely_benign	0.1546	benign	-0.309	Destabilizing	0.013	N	0.173	neutral	None	None	None	None	N
E/V	0.1441	likely_benign	0.1613	benign	0.009	Stabilizing	0.642	D	0.339	neutral	N	0.508779038	None	None	N
E/W	0.7972	likely_pathogenic	0.847	pathogenic	0.07	Stabilizing	0.995	D	0.273	neutral	None	None	None	None	N
E/Y	0.5057	ambiguous	0.5839	pathogenic	0.125	Stabilizing	0.981	D	0.312	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.