TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20714	62365;62366;62367	chr2:178589585;178589584;178589583	chr2:179454312;179454311;179454310
N2AB	19073	57442;57443;57444	chr2:178589585;178589584;178589583	chr2:179454312;179454311;179454310
N2A	18146	54661;54662;54663	chr2:178589585;178589584;178589583	chr2:179454312;179454311;179454310
N2B	11649	35170;35171;35172	chr2:178589585;178589584;178589583	chr2:179454312;179454311;179454310
Novex-1	11774	35545;35546;35547	chr2:178589585;178589584;178589583	chr2:179454312;179454311;179454310
Novex-2	11841	35746;35747;35748	chr2:178589585;178589584;178589583	chr2:179454312;179454311;179454310
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: Fn3-38
• Domain position: 47
• Structural Position: 64
• Q(SASA): 0.5882
• 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
D/E	None	None	None	N	0.117	0.07	0.166414681773	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
D/A	0.0855	likely_benign	0.1252	benign	-0.153	Destabilizing	0.003	N	0.185	neutral	N	0.425475427	None	None	N
D/C	0.357	ambiguous	0.5651	pathogenic	-0.122	Destabilizing	0.983	D	0.351	neutral	None	None	None	None	N
D/E	0.0707	likely_benign	0.102	benign	-0.238	Destabilizing	None	N	0.117	neutral	N	0.377604122	None	None	N
D/F	0.3256	likely_benign	0.5148	ambiguous	-0.14	Destabilizing	0.94	D	0.353	neutral	None	None	None	None	N
D/G	0.1099	likely_benign	0.1737	benign	-0.297	Destabilizing	0.101	N	0.325	neutral	N	0.441135526	None	None	N
D/H	0.1597	likely_benign	0.2551	benign	0.366	Stabilizing	0.794	D	0.276	neutral	N	0.448968362	None	None	N
D/I	0.1302	likely_benign	0.1966	benign	0.169	Stabilizing	0.836	D	0.372	neutral	None	None	None	None	N
D/K	0.1416	likely_benign	0.2238	benign	0.346	Stabilizing	0.129	N	0.327	neutral	None	None	None	None	N
D/L	0.1707	likely_benign	0.2449	benign	0.169	Stabilizing	0.418	N	0.361	neutral	None	None	None	None	N
D/M	0.2763	likely_benign	0.4393	ambiguous	0.078	Stabilizing	0.94	D	0.351	neutral	None	None	None	None	N
D/N	0.0736	likely_benign	0.102	benign	0.105	Stabilizing	0.351	N	0.296	neutral	N	0.4505258	None	None	N
D/P	0.6055	likely_pathogenic	0.7165	pathogenic	0.082	Stabilizing	0.593	D	0.313	neutral	None	None	None	None	N
D/Q	0.1339	likely_benign	0.2151	benign	0.119	Stabilizing	0.027	N	0.163	neutral	None	None	None	None	N
D/R	0.1999	likely_benign	0.3208	benign	0.609	Stabilizing	0.418	N	0.363	neutral	None	None	None	None	N
D/S	0.0784	likely_benign	0.105	benign	-0.019	Destabilizing	0.129	N	0.329	neutral	None	None	None	None	N
D/T	0.093	likely_benign	0.1358	benign	0.1	Stabilizing	0.418	N	0.33	neutral	None	None	None	None	N
D/V	0.0891	likely_benign	0.1198	benign	0.082	Stabilizing	0.351	N	0.361	neutral	N	0.451392592	None	None	N
D/W	0.7383	likely_pathogenic	0.8643	pathogenic	-0.041	Destabilizing	0.983	D	0.378	neutral	None	None	None	None	N
D/Y	0.1594	likely_benign	0.251	benign	0.097	Stabilizing	0.921	D	0.356	neutral	N	0.497703672	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.