TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26001	78226;78227;78228	chr2:178568131;178568130;178568129	chr2:179432858;179432857;179432856
N2AB	24360	73303;73304;73305	chr2:178568131;178568130;178568129	chr2:179432858;179432857;179432856
N2A	23433	70522;70523;70524	chr2:178568131;178568130;178568129	chr2:179432858;179432857;179432856
N2B	16936	51031;51032;51033	chr2:178568131;178568130;178568129	chr2:179432858;179432857;179432856
Novex-1	17061	51406;51407;51408	chr2:178568131;178568130;178568129	chr2:179432858;179432857;179432856
Novex-2	17128	51607;51608;51609	chr2:178568131;178568130;178568129	chr2:179432858;179432857;179432856
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Fn3-77
• Domain position: 12
• Structural Position: 14
• Q(SASA): 0.3665
• 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
A/V	rs774218394	0.123	None	N	0.095	0.131	0.287603790349	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	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
A/C	0.2828	likely_benign	0.269	benign	-0.788	Destabilizing	0.824	D	0.395	neutral	None	None	None	None	N
A/D	0.1964	likely_benign	0.1893	benign	-0.168	Destabilizing	0.062	N	0.499	neutral	N	0.410177901	None	None	N
A/E	0.1957	likely_benign	0.1963	benign	-0.301	Destabilizing	0.001	N	0.193	neutral	None	None	None	None	N
A/F	0.1625	likely_benign	0.1843	benign	-0.748	Destabilizing	0.38	N	0.499	neutral	None	None	None	None	N
A/G	0.111	likely_benign	0.1022	benign	-0.361	Destabilizing	0.117	N	0.359	neutral	N	0.485118377	None	None	N
A/H	0.2725	likely_benign	0.27	benign	-0.375	Destabilizing	0.824	D	0.447	neutral	None	None	None	None	N
A/I	0.136	likely_benign	0.1571	benign	-0.235	Destabilizing	0.001	N	0.197	neutral	None	None	None	None	N
A/K	0.3399	likely_benign	0.3392	benign	-0.596	Destabilizing	0.081	N	0.381	neutral	None	None	None	None	N
A/L	0.1073	likely_benign	0.1106	benign	-0.235	Destabilizing	0.035	N	0.406	neutral	None	None	None	None	N
A/M	0.1257	likely_benign	0.132	benign	-0.335	Destabilizing	0.38	N	0.396	neutral	None	None	None	None	N
A/N	0.1291	likely_benign	0.1267	benign	-0.322	Destabilizing	0.38	N	0.491	neutral	None	None	None	None	N
A/P	0.7192	likely_pathogenic	0.7464	pathogenic	-0.212	Destabilizing	0.484	N	0.418	neutral	N	0.494796652	None	None	N
A/Q	0.2287	likely_benign	0.2231	benign	-0.554	Destabilizing	0.235	N	0.423	neutral	None	None	None	None	N
A/R	0.3178	likely_benign	0.3192	benign	-0.197	Destabilizing	0.38	N	0.417	neutral	None	None	None	None	N
A/S	0.0713	likely_benign	0.0698	benign	-0.599	Destabilizing	0.005	N	0.185	neutral	N	0.403617288	None	None	N
A/T	0.0673	likely_benign	0.0681	benign	-0.64	Destabilizing	0.001	N	0.061	neutral	N	0.458433208	None	None	N
A/V	0.088	likely_benign	0.0988	benign	-0.212	Destabilizing	None	N	0.095	neutral	N	0.508707312	None	None	N
A/W	0.5476	ambiguous	0.565	pathogenic	-0.912	Destabilizing	0.935	D	0.545	neutral	None	None	None	None	N
A/Y	0.2513	likely_benign	0.2582	benign	-0.547	Destabilizing	0.555	D	0.492	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.