TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3991	12196;12197;12198	chr2:178741262;178741261;178741260	chr2:179605989;179605988;179605987
N2AB	3674	11245;11246;11247	chr2:178741262;178741261;178741260	chr2:179605989;179605988;179605987
N2A	None	None	chr2:None	chr2:None
N2B	3628	11107;11108;11109	chr2:178741262;178741261;178741260	chr2:179605989;179605988;179605987
Novex-1	3753	11482;11483;11484	chr2:178741262;178741261;178741260	chr2:179605989;179605988;179605987
Novex-2	3820	11683;11684;11685	chr2:178741262;178741261;178741260	chr2:179605989;179605988;179605987
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-28
• Domain position: 54
• Structural Position: 131
• Q(SASA): 0.7798
• 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
N/S	rs1248393743	None	0.005	N	0.213	0.166	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
N/S	rs1248393743	None	0.005	N	0.213	0.166	None	gnomAD-4.0.0	3.09863E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.23794E-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
N/A	0.1482	likely_benign	0.1318	benign	-0.253	Destabilizing	0.016	N	0.405	neutral	None	None	None	None	N
N/C	0.2171	likely_benign	0.2062	benign	0.498	Stabilizing	0.864	D	0.391	neutral	None	None	None	None	N
N/D	0.0484	likely_benign	0.0489	benign	0.002	Stabilizing	None	N	0.162	neutral	N	0.363264421	None	None	N
N/E	0.2081	likely_benign	0.1828	benign	-0.055	Destabilizing	None	N	0.16	neutral	None	None	None	None	N
N/F	0.4659	ambiguous	0.4075	ambiguous	-0.747	Destabilizing	0.628	D	0.439	neutral	None	None	None	None	N
N/G	0.1741	likely_benign	0.1555	benign	-0.386	Destabilizing	0.014	N	0.223	neutral	None	None	None	None	N
N/H	0.1369	likely_benign	0.125	benign	-0.495	Destabilizing	0.295	N	0.3	neutral	N	0.447511746	None	None	N
N/I	0.1927	likely_benign	0.1775	benign	0.006	Stabilizing	0.106	N	0.449	neutral	D	0.527576333	None	None	N
N/K	0.2325	likely_benign	0.2119	benign	0.182	Stabilizing	0.012	N	0.243	neutral	N	0.451296477	None	None	N
N/L	0.2145	likely_benign	0.2039	benign	0.006	Stabilizing	0.072	N	0.463	neutral	None	None	None	None	N
N/M	0.2944	likely_benign	0.284	benign	0.43	Stabilizing	0.628	D	0.413	neutral	None	None	None	None	N
N/P	0.6785	likely_pathogenic	0.6424	pathogenic	-0.056	Destabilizing	0.136	N	0.448	neutral	None	None	None	None	N
N/Q	0.2692	likely_benign	0.2462	benign	-0.169	Destabilizing	0.016	N	0.265	neutral	None	None	None	None	N
N/R	0.2774	likely_benign	0.2402	benign	0.273	Stabilizing	0.038	N	0.267	neutral	None	None	None	None	N
N/S	0.0737	likely_benign	0.0708	benign	0.097	Stabilizing	0.005	N	0.213	neutral	N	0.442646312	None	None	N
N/T	0.109	likely_benign	0.1037	benign	0.161	Stabilizing	0.024	N	0.255	neutral	N	0.447263231	None	None	N
N/V	0.1617	likely_benign	0.1459	benign	-0.056	Destabilizing	0.072	N	0.463	neutral	None	None	None	None	N
N/W	0.7252	likely_pathogenic	0.6862	pathogenic	-0.792	Destabilizing	0.864	D	0.409	neutral	None	None	None	None	N
N/Y	0.1564	likely_benign	0.1361	benign	-0.506	Destabilizing	0.56	D	0.439	neutral	N	0.442165428	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.