TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23393	70402;70403;70404	chr2:178575955;178575954;178575953	chr2:179440682;179440681;179440680
N2AB	21752	65479;65480;65481	chr2:178575955;178575954;178575953	chr2:179440682;179440681;179440680
N2A	20825	62698;62699;62700	chr2:178575955;178575954;178575953	chr2:179440682;179440681;179440680
N2B	14328	43207;43208;43209	chr2:178575955;178575954;178575953	chr2:179440682;179440681;179440680
Novex-1	14453	43582;43583;43584	chr2:178575955;178575954;178575953	chr2:179440682;179440681;179440680
Novex-2	14520	43783;43784;43785	chr2:178575955;178575954;178575953	chr2:179440682;179440681;179440680
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-129
• Domain position: 49
• Structural Position: 127
• Q(SASA): 0.4434
• 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/K	rs1040909022	None	0.379	N	0.361	0.166	0.0846915920261	gnomAD-4.0.0	1.59653E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43402E-05	0
N/T	rs1709929760	None	0.007	N	0.267	0.101	0.193865811164	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	4.1425E-04	0
N/T	rs1709929760	None	0.007	N	0.267	0.101	0.193865811164	gnomAD-4.0.0	1.31463E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	4.1425E-04	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	0.2842	likely_benign	0.3137	benign	-0.755	Destabilizing	0.25	N	0.529	neutral	None	None	None	None	N
N/C	0.2718	likely_benign	0.2946	benign	0.153	Stabilizing	0.992	D	0.546	neutral	None	None	None	None	N
N/D	0.2141	likely_benign	0.243	benign	0.031	Stabilizing	0.549	D	0.326	neutral	N	0.505699585	None	None	N
N/E	0.4875	ambiguous	0.5379	ambiguous	0.08	Stabilizing	0.617	D	0.359	neutral	None	None	None	None	N
N/F	0.6499	likely_pathogenic	0.6993	pathogenic	-0.693	Destabilizing	0.92	D	0.561	neutral	None	None	None	None	N
N/G	0.4174	ambiguous	0.4544	ambiguous	-1.045	Destabilizing	0.25	N	0.359	neutral	None	None	None	None	N
N/H	0.1636	likely_benign	0.1738	benign	-0.839	Destabilizing	0.896	D	0.486	neutral	D	0.535675775	None	None	N
N/I	0.2069	likely_benign	0.2257	benign	-0.045	Destabilizing	0.379	N	0.52	neutral	N	0.508123814	None	None	N
N/K	0.441	ambiguous	0.4743	ambiguous	-0.072	Destabilizing	0.379	N	0.361	neutral	N	0.51526043	None	None	N
N/L	0.3287	likely_benign	0.3648	ambiguous	-0.045	Destabilizing	0.25	N	0.535	neutral	None	None	None	None	N
N/M	0.301	likely_benign	0.327	benign	0.351	Stabilizing	0.92	D	0.536	neutral	None	None	None	None	N
N/P	0.7804	likely_pathogenic	0.8119	pathogenic	-0.252	Destabilizing	0.92	D	0.521	neutral	None	None	None	None	N
N/Q	0.4315	ambiguous	0.4661	ambiguous	-0.593	Destabilizing	0.85	D	0.45	neutral	None	None	None	None	N
N/R	0.5349	ambiguous	0.5814	pathogenic	-0.083	Destabilizing	0.85	D	0.432	neutral	None	None	None	None	N
N/S	0.1076	likely_benign	0.1078	benign	-0.586	Destabilizing	0.016	N	0.252	neutral	N	0.468912065	None	None	N
N/T	0.1046	likely_benign	0.1053	benign	-0.35	Destabilizing	0.007	N	0.267	neutral	N	0.430471107	None	None	N
N/V	0.203	likely_benign	0.2166	benign	-0.252	Destabilizing	0.021	N	0.443	neutral	None	None	None	None	N
N/W	0.8609	likely_pathogenic	0.888	pathogenic	-0.48	Destabilizing	0.992	D	0.591	neutral	None	None	None	None	N
N/Y	0.2219	likely_benign	0.2441	benign	-0.28	Destabilizing	0.963	D	0.546	neutral	D	0.528440371	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.