TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21315	64168;64169;64170	chr2:178587268;178587267;178587266	chr2:179451995;179451994;179451993
N2AB	19674	59245;59246;59247	chr2:178587268;178587267;178587266	chr2:179451995;179451994;179451993
N2A	18747	56464;56465;56466	chr2:178587268;178587267;178587266	chr2:179451995;179451994;179451993
N2B	12250	36973;36974;36975	chr2:178587268;178587267;178587266	chr2:179451995;179451994;179451993
Novex-1	12375	37348;37349;37350	chr2:178587268;178587267;178587266	chr2:179451995;179451994;179451993
Novex-2	12442	37549;37550;37551	chr2:178587268;178587267;178587266	chr2:179451995;179451994;179451993
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Fn3-42
• Domain position: 50
• Structural Position: 67
• Q(SASA): 0.339
• 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
T/N	rs747246624	-0.671	0.006	N	0.2	0.085	0.17948927462	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	5.8E-05	None	0	0	None	0	None	0	8.92E-06	0
T/N	rs747246624	-0.671	0.006	N	0.2	0.085	0.17948927462	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	0	1.96747E-04	0	0	0	None	0	0	0	0	0
T/N	rs747246624	-0.671	0.006	N	0.2	0.085	0.17948927462	gnomAD-4.0.0	5.57954E-06	None	None	None	None	N	None	0	6.67334E-05	None	0	0	None	0	0	4.23912E-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
T/A	0.0764	likely_benign	0.0701	benign	-0.722	Destabilizing	0.09	N	0.333	neutral	N	0.496951523	None	None	N
T/C	0.3336	likely_benign	0.302	benign	-0.458	Destabilizing	0.944	D	0.513	neutral	None	None	None	None	N
T/D	0.5985	likely_pathogenic	0.5293	ambiguous	-0.178	Destabilizing	0.241	N	0.437	neutral	None	None	None	None	N
T/E	0.4735	ambiguous	0.411	ambiguous	-0.199	Destabilizing	0.388	N	0.447	neutral	None	None	None	None	N
T/F	0.2938	likely_benign	0.2593	benign	-0.85	Destabilizing	0.69	D	0.537	neutral	None	None	None	None	N
T/G	0.292	likely_benign	0.2579	benign	-0.957	Destabilizing	0.388	N	0.463	neutral	None	None	None	None	N
T/H	0.3436	ambiguous	0.2974	benign	-1.256	Destabilizing	0.818	D	0.521	neutral	None	None	None	None	N
T/I	0.1384	likely_benign	0.1202	benign	-0.196	Destabilizing	0.001	N	0.283	neutral	N	0.507419233	None	None	N
T/K	0.3186	likely_benign	0.2707	benign	-0.756	Destabilizing	0.004	N	0.217	neutral	None	None	None	None	N
T/L	0.0878	likely_benign	0.0771	benign	-0.196	Destabilizing	0.043	N	0.45	neutral	None	None	None	None	N
T/M	0.0876	likely_benign	0.0838	benign	0.081	Stabilizing	0.69	D	0.533	neutral	None	None	None	None	N
T/N	0.1581	likely_benign	0.135	benign	-0.623	Destabilizing	0.006	N	0.2	neutral	N	0.485638452	None	None	N
T/P	0.1102	likely_benign	0.0988	benign	-0.339	Destabilizing	0.912	D	0.545	neutral	N	0.465687254	None	None	N
T/Q	0.2967	likely_benign	0.2532	benign	-0.818	Destabilizing	0.69	D	0.547	neutral	None	None	None	None	N
T/R	0.267	likely_benign	0.2256	benign	-0.487	Destabilizing	0.241	N	0.499	neutral	None	None	None	None	N
T/S	0.1269	likely_benign	0.1139	benign	-0.884	Destabilizing	0.165	N	0.364	neutral	N	0.505338933	None	None	N
T/V	0.1011	likely_benign	0.0879	benign	-0.339	Destabilizing	0.002	N	0.132	neutral	None	None	None	None	N
T/W	0.6819	likely_pathogenic	0.6542	pathogenic	-0.787	Destabilizing	0.981	D	0.552	neutral	None	None	None	None	N
T/Y	0.352	ambiguous	0.3116	benign	-0.563	Destabilizing	0.818	D	0.54	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.