TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2705	8338;8339;8340	chr2:178771214;178771213;178771212	chr2:179635941;179635940;179635939
N2AB	2705	8338;8339;8340	chr2:178771214;178771213;178771212	chr2:179635941;179635940;179635939
N2A	2705	8338;8339;8340	chr2:178771214;178771213;178771212	chr2:179635941;179635940;179635939
N2B	2659	8200;8201;8202	chr2:178771214;178771213;178771212	chr2:179635941;179635940;179635939
Novex-1	2659	8200;8201;8202	chr2:178771214;178771213;178771212	chr2:179635941;179635940;179635939
Novex-2	2659	8200;8201;8202	chr2:178771214;178771213;178771212	chr2:179635941;179635940;179635939
Novex-3	2705	8338;8339;8340	chr2:178771214;178771213;178771212	chr2:179635941;179635940;179635939

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-16
• Domain position: 85
• Structural Position: 177
• Q(SASA): 0.6639
• 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	0.999	N	0.547	0.323	0.211220785272	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
E/A	0.3454	ambiguous	0.4155	ambiguous	-0.445	Destabilizing	0.999	D	0.509	neutral	N	0.440740568	None	None	N
E/C	0.9714	likely_pathogenic	0.9785	pathogenic	-0.159	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
E/D	0.4072	ambiguous	0.4729	ambiguous	-0.6	Destabilizing	0.999	D	0.433	neutral	N	0.362898684	None	None	N
E/F	0.9308	likely_pathogenic	0.9488	pathogenic	-0.223	Destabilizing	1.0	D	0.671	neutral	None	None	None	None	N
E/G	0.5075	ambiguous	0.5908	pathogenic	-0.688	Destabilizing	1.0	D	0.536	neutral	N	0.477621434	None	None	N
E/H	0.7858	likely_pathogenic	0.8463	pathogenic	-0.103	Destabilizing	1.0	D	0.611	neutral	None	None	None	None	N
E/I	0.6693	likely_pathogenic	0.711	pathogenic	0.174	Stabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	N
E/K	0.3399	likely_benign	0.431	ambiguous	0.1	Stabilizing	0.999	D	0.547	neutral	N	0.322675325	None	None	N
E/L	0.694	likely_pathogenic	0.7475	pathogenic	0.174	Stabilizing	1.0	D	0.654	neutral	None	None	None	None	N
E/M	0.7269	likely_pathogenic	0.7662	pathogenic	0.278	Stabilizing	1.0	D	0.623	neutral	None	None	None	None	N
E/N	0.622	likely_pathogenic	0.6943	pathogenic	-0.26	Destabilizing	1.0	D	0.597	neutral	None	None	None	None	N
E/P	0.9657	likely_pathogenic	0.9764	pathogenic	-0.011	Destabilizing	1.0	D	0.557	neutral	None	None	None	None	N
E/Q	0.2792	likely_benign	0.3349	benign	-0.216	Destabilizing	1.0	D	0.493	neutral	N	0.329701795	None	None	N
E/R	0.5473	ambiguous	0.6502	pathogenic	0.362	Stabilizing	1.0	D	0.592	neutral	None	None	None	None	N
E/S	0.4782	ambiguous	0.5512	ambiguous	-0.44	Destabilizing	0.999	D	0.521	neutral	None	None	None	None	N
E/T	0.4476	ambiguous	0.4896	ambiguous	-0.247	Destabilizing	1.0	D	0.565	neutral	None	None	None	None	N
E/V	0.4229	ambiguous	0.468	ambiguous	-0.011	Destabilizing	1.0	D	0.599	neutral	N	0.354980159	None	None	N
E/W	0.9807	likely_pathogenic	0.9855	pathogenic	-0.05	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
E/Y	0.9068	likely_pathogenic	0.933	pathogenic	0.024	Stabilizing	1.0	D	0.62	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.