TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31179	93760;93761;93762	chr2:178548091;178548090;178548089	chr2:179412818;179412817;179412816
N2AB	29538	88837;88838;88839	chr2:178548091;178548090;178548089	chr2:179412818;179412817;179412816
N2A	28611	86056;86057;86058	chr2:178548091;178548090;178548089	chr2:179412818;179412817;179412816
N2B	22114	66565;66566;66567	chr2:178548091;178548090;178548089	chr2:179412818;179412817;179412816
Novex-1	22239	66940;66941;66942	chr2:178548091;178548090;178548089	chr2:179412818;179412817;179412816
Novex-2	22306	67141;67142;67143	chr2:178548091;178548090;178548089	chr2:179412818;179412817;179412816
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-115
• Domain position: 67
• Structural Position: 100
• Q(SASA): 0.7587
• 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
K/N	rs776904754	0.236	None	N	0.213	0.11	0.0846915920261	gnomAD-2.1.1	1.2E-05	None	None	None	None	N	None	0	0	None	0	0	None	9.8E-05	None	0	0	0
K/N	rs776904754	0.236	None	N	0.213	0.11	0.0846915920261	gnomAD-4.0.0	4.78925E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.95588E-05	1.65656E-05

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
K/A	0.1718	likely_benign	0.1766	benign	0.029	Stabilizing	0.031	N	0.442	neutral	None	None	None	None	N
K/C	0.3553	ambiguous	0.3637	ambiguous	-0.305	Destabilizing	0.864	D	0.447	neutral	None	None	None	None	N
K/D	0.1093	likely_benign	0.0985	benign	0.042	Stabilizing	0.007	N	0.379	neutral	None	None	None	None	N
K/E	0.1117	likely_benign	0.1034	benign	0.078	Stabilizing	0.005	N	0.277	neutral	N	0.419952177	None	None	N
K/F	0.53	ambiguous	0.556	ambiguous	-0.038	Destabilizing	0.628	D	0.464	neutral	None	None	None	None	N
K/G	0.1123	likely_benign	0.1091	benign	-0.206	Destabilizing	0.007	N	0.417	neutral	None	None	None	None	N
K/H	0.11	likely_benign	0.112	benign	-0.391	Destabilizing	0.214	N	0.448	neutral	None	None	None	None	N
K/I	0.3887	ambiguous	0.3885	ambiguous	0.58	Stabilizing	0.295	N	0.493	neutral	N	0.5068218	None	None	N
K/L	0.213	likely_benign	0.2268	benign	0.58	Stabilizing	0.031	N	0.497	neutral	None	None	None	None	N
K/M	0.1481	likely_benign	0.1492	benign	0.183	Stabilizing	0.628	D	0.437	neutral	None	None	None	None	N
K/N	0.0529	likely_benign	0.0488	benign	0.059	Stabilizing	None	N	0.213	neutral	N	0.329735605	None	None	N
K/P	0.7197	likely_pathogenic	0.7108	pathogenic	0.425	Stabilizing	0.136	N	0.488	neutral	None	None	None	None	N
K/Q	0.0892	likely_benign	0.0913	benign	-0.043	Destabilizing	0.055	N	0.392	neutral	N	0.43501763	None	None	N
K/R	0.0881	likely_benign	0.0899	benign	-0.102	Destabilizing	0.024	N	0.397	neutral	N	0.457913133	None	None	N
K/S	0.1143	likely_benign	0.1094	benign	-0.408	Destabilizing	0.007	N	0.267	neutral	None	None	None	None	N
K/T	0.1217	likely_benign	0.1208	benign	-0.212	Destabilizing	0.012	N	0.461	neutral	N	0.4370765	None	None	N
K/V	0.3221	likely_benign	0.332	benign	0.425	Stabilizing	0.136	N	0.525	neutral	None	None	None	None	N
K/W	0.5939	likely_pathogenic	0.5946	pathogenic	-0.068	Destabilizing	0.864	D	0.463	neutral	None	None	None	None	N
K/Y	0.2486	likely_benign	0.2398	benign	0.272	Stabilizing	0.628	D	0.485	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.