TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23446	70561;70562;70563	chr2:178575796;178575795;178575794	chr2:179440523;179440522;179440521
N2AB	21805	65638;65639;65640	chr2:178575796;178575795;178575794	chr2:179440523;179440522;179440521
N2A	20878	62857;62858;62859	chr2:178575796;178575795;178575794	chr2:179440523;179440522;179440521
N2B	14381	43366;43367;43368	chr2:178575796;178575795;178575794	chr2:179440523;179440522;179440521
Novex-1	14506	43741;43742;43743	chr2:178575796;178575795;178575794	chr2:179440523;179440522;179440521
Novex-2	14573	43942;43943;43944	chr2:178575796;178575795;178575794	chr2:179440523;179440522;179440521
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: Fn3-58
• Domain position: 12
• Structural Position: 14
• Q(SASA): 0.4906
• 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/A	None	None	0.338	N	0.464	0.311	0.344945010812	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
D/N	rs1290459779	0.399	0.505	N	0.443	0.218	0.193865811164	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	9.96E-05	0	None	0	None	0	0	0
D/N	rs1290459779	0.399	0.505	N	0.443	0.218	0.193865811164	gnomAD-4.0.0	1.59285E-06	None	None	None	None	N	None	0	0	None	4.76872E-05	0	None	0	0	0	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	0.1107	likely_benign	0.1465	benign	-0.343	Destabilizing	0.338	N	0.464	neutral	N	0.502992061	None	None	N
D/C	0.541	ambiguous	0.6114	pathogenic	0.085	Stabilizing	0.991	D	0.653	neutral	None	None	None	None	N
D/E	0.0862	likely_benign	0.1018	benign	-0.335	Destabilizing	None	N	0.076	neutral	N	0.408215031	None	None	N
D/F	0.5502	ambiguous	0.6433	pathogenic	-0.329	Destabilizing	0.967	D	0.604	neutral	None	None	None	None	N
D/G	0.1706	likely_benign	0.1944	benign	-0.56	Destabilizing	0.505	D	0.439	neutral	N	0.514459849	None	None	N
D/H	0.2704	likely_benign	0.2972	benign	-0.345	Destabilizing	0.879	D	0.525	neutral	N	0.475878689	None	None	N
D/I	0.3205	likely_benign	0.4115	ambiguous	0.184	Stabilizing	0.906	D	0.598	neutral	None	None	None	None	N
D/K	0.3391	likely_benign	0.3856	ambiguous	0.184	Stabilizing	0.404	N	0.423	neutral	None	None	None	None	N
D/L	0.3383	likely_benign	0.4105	ambiguous	0.184	Stabilizing	0.826	D	0.523	neutral	None	None	None	None	N
D/M	0.4653	ambiguous	0.5581	ambiguous	0.447	Stabilizing	0.991	D	0.597	neutral	None	None	None	None	N
D/N	0.0883	likely_benign	0.0992	benign	-0.068	Destabilizing	0.505	D	0.443	neutral	N	0.500490474	None	None	N
D/P	0.9185	likely_pathogenic	0.9345	pathogenic	0.031	Stabilizing	0.906	D	0.469	neutral	None	None	None	None	N
D/Q	0.2449	likely_benign	0.2755	benign	-0.028	Destabilizing	0.404	N	0.444	neutral	None	None	None	None	N
D/R	0.4021	ambiguous	0.4463	ambiguous	0.293	Stabilizing	0.826	D	0.5	neutral	None	None	None	None	N
D/S	0.1046	likely_benign	0.126	benign	-0.199	Destabilizing	0.404	N	0.397	neutral	None	None	None	None	N
D/T	0.1841	likely_benign	0.2291	benign	-0.034	Destabilizing	0.575	D	0.48	neutral	None	None	None	None	N
D/V	0.1848	likely_benign	0.2475	benign	0.031	Stabilizing	0.782	D	0.524	neutral	N	0.480371687	None	None	N
D/W	0.8938	likely_pathogenic	0.9147	pathogenic	-0.216	Destabilizing	0.991	D	0.673	neutral	None	None	None	None	N
D/Y	0.2683	likely_benign	0.3242	benign	-0.104	Destabilizing	0.957	D	0.608	neutral	D	0.522620584	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.