TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23032	69319;69320;69321	chr2:178577241;178577240;178577239	chr2:179441968;179441967;179441966
N2AB	21391	64396;64397;64398	chr2:178577241;178577240;178577239	chr2:179441968;179441967;179441966
N2A	20464	61615;61616;61617	chr2:178577241;178577240;178577239	chr2:179441968;179441967;179441966
N2B	13967	42124;42125;42126	chr2:178577241;178577240;178577239	chr2:179441968;179441967;179441966
Novex-1	14092	42499;42500;42501	chr2:178577241;178577240;178577239	chr2:179441968;179441967;179441966
Novex-2	14159	42700;42701;42702	chr2:178577241;178577240;178577239	chr2:179441968;179441967;179441966
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Ig-128
• Domain position: 83
• Structural Position: 171
• Q(SASA): 0.5511
• 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
H/D	None	None	0.166	N	0.389	0.235	0.223146558224	gnomAD-4.0.0	1.59271E-06	None	None	None	None	N	None	0	0	None	0	2.78753E-05	None	0	0	0	0	0
H/L	rs886055251	None	0.166	N	0.441	0.317	0.432716982437	gnomAD-4.0.0	1.5927E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86E-06	0	0
H/Q	rs1374973500	0.175	0.491	N	0.412	0.117	0.270001397563	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
H/Q	rs1374973500	0.175	0.491	N	0.412	0.117	0.270001397563	gnomAD-4.0.0	6.84475E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.9964E-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
H/A	0.1681	likely_benign	0.1531	benign	0.333	Stabilizing	0.002	N	0.393	neutral	None	None	None	None	N
H/C	0.1428	likely_benign	0.1241	benign	0.907	Stabilizing	0.901	D	0.555	neutral	None	None	None	None	N
H/D	0.1456	likely_benign	0.1347	benign	0.031	Stabilizing	0.166	N	0.389	neutral	N	0.428910882	None	None	N
H/E	0.2111	likely_benign	0.183	benign	0.064	Stabilizing	0.345	N	0.318	neutral	None	None	None	None	N
H/F	0.3092	likely_benign	0.2841	benign	1.021	Stabilizing	0.901	D	0.595	neutral	None	None	None	None	N
H/G	0.2156	likely_benign	0.2003	benign	0.029	Stabilizing	0.209	N	0.413	neutral	None	None	None	None	N
H/I	0.2333	likely_benign	0.2065	benign	1.117	Stabilizing	0.561	D	0.598	neutral	None	None	None	None	N
H/K	0.1362	likely_benign	0.1285	benign	0.284	Stabilizing	0.007	N	0.256	neutral	None	None	None	None	N
H/L	0.1092	likely_benign	0.1027	benign	1.117	Stabilizing	0.166	N	0.441	neutral	N	0.484630879	None	None	N
H/M	0.3049	likely_benign	0.2923	benign	0.892	Stabilizing	0.965	D	0.569	neutral	None	None	None	None	N
H/N	0.0629	likely_benign	0.0635	benign	0.362	Stabilizing	0.005	N	0.209	neutral	N	0.418752604	None	None	N
H/P	0.1552	likely_benign	0.1349	benign	0.882	Stabilizing	0.662	D	0.559	neutral	N	0.478070266	None	None	N
H/Q	0.1337	likely_benign	0.1248	benign	0.487	Stabilizing	0.491	N	0.412	neutral	N	0.479358345	None	None	N
H/R	0.0875	likely_benign	0.0814	benign	-0.394	Destabilizing	0.166	N	0.342	neutral	N	0.464908968	None	None	N
H/S	0.1361	likely_benign	0.1286	benign	0.494	Stabilizing	0.007	N	0.268	neutral	None	None	None	None	N
H/T	0.1203	likely_benign	0.108	benign	0.624	Stabilizing	0.007	N	0.363	neutral	None	None	None	None	N
H/V	0.179	likely_benign	0.1623	benign	0.882	Stabilizing	0.209	N	0.444	neutral	None	None	None	None	N
H/W	0.4207	ambiguous	0.3988	ambiguous	1.012	Stabilizing	0.991	D	0.579	neutral	None	None	None	None	N
H/Y	0.1204	likely_benign	0.1082	benign	1.305	Stabilizing	0.856	D	0.471	neutral	N	0.49332772	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.