TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14094	42505;42506;42507	chr2:178634501;178634500;178634499	chr2:179499228;179499227;179499226
N2AB	12453	37582;37583;37584	chr2:178634501;178634500;178634499	chr2:179499228;179499227;179499226
N2A	11526	34801;34802;34803	chr2:178634501;178634500;178634499	chr2:179499228;179499227;179499226
N2B	5029	15310;15311;15312	chr2:178634501;178634500;178634499	chr2:179499228;179499227;179499226
Novex-1	5154	15685;15686;15687	chr2:178634501;178634500;178634499	chr2:179499228;179499227;179499226
Novex-2	5221	15886;15887;15888	chr2:178634501;178634500;178634499	chr2:179499228;179499227;179499226
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Ig-91
• Domain position: 41
• Structural Position: 70
• Q(SASA): 0.6278
• 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
S/P	None	None	None	N	0.155	0.163	0.0666544352282	gnomAD-4.0.0	1.3688E-06	None	None	None	None	N	None	2.9915E-05	0	None	0	0	None	0	0	8.99659E-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
S/A	0.0489	likely_benign	0.0515	benign	-0.253	Destabilizing	None	N	0.129	neutral	N	0.481441926	None	None	N
S/C	0.1721	likely_benign	0.1909	benign	-0.33	Destabilizing	0.356	N	0.332	neutral	None	None	None	None	N
S/D	0.3802	ambiguous	0.4034	ambiguous	0.237	Stabilizing	0.031	N	0.168	neutral	None	None	None	None	N
S/E	0.3903	ambiguous	0.4282	ambiguous	0.141	Stabilizing	0.016	N	0.193	neutral	None	None	None	None	N
S/F	0.2743	likely_benign	0.3203	benign	-0.925	Destabilizing	0.214	N	0.475	neutral	None	None	None	None	N
S/G	0.0998	likely_benign	0.0996	benign	-0.338	Destabilizing	0.016	N	0.181	neutral	None	None	None	None	N
S/H	0.3918	ambiguous	0.4145	ambiguous	-0.783	Destabilizing	0.356	N	0.325	neutral	None	None	None	None	N
S/I	0.1877	likely_benign	0.2118	benign	-0.163	Destabilizing	None	N	0.194	neutral	None	None	None	None	N
S/K	0.5439	ambiguous	0.5593	ambiguous	-0.394	Destabilizing	0.016	N	0.179	neutral	None	None	None	None	N
S/L	0.126	likely_benign	0.1451	benign	-0.163	Destabilizing	0.005	N	0.247	neutral	N	0.514078866	None	None	N
S/M	0.2154	likely_benign	0.2312	benign	-0.084	Destabilizing	0.214	N	0.332	neutral	None	None	None	None	N
S/N	0.1742	likely_benign	0.1706	benign	-0.166	Destabilizing	0.136	N	0.214	neutral	None	None	None	None	N
S/P	0.0863	likely_benign	0.0883	benign	-0.165	Destabilizing	None	N	0.155	neutral	N	0.404209194	None	None	N
S/Q	0.3987	ambiguous	0.422	ambiguous	-0.37	Destabilizing	0.003	N	0.155	neutral	None	None	None	None	N
S/R	0.5085	ambiguous	0.547	ambiguous	-0.21	Destabilizing	0.072	N	0.358	neutral	None	None	None	None	N
S/T	0.0907	likely_benign	0.0992	benign	-0.259	Destabilizing	None	N	0.133	neutral	N	0.503447892	None	None	N
S/V	0.1552	likely_benign	0.1768	benign	-0.165	Destabilizing	None	N	0.152	neutral	None	None	None	None	N
S/W	0.4399	ambiguous	0.483	ambiguous	-0.982	Destabilizing	0.864	D	0.391	neutral	None	None	None	None	N
S/Y	0.2277	likely_benign	0.2452	benign	-0.67	Destabilizing	0.356	N	0.465	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.