TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30662	92209;92210;92211	chr2:178549738;178549737;178549736	chr2:179414465;179414464;179414463
N2AB	29021	87286;87287;87288	chr2:178549738;178549737;178549736	chr2:179414465;179414464;179414463
N2A	28094	84505;84506;84507	chr2:178549738;178549737;178549736	chr2:179414465;179414464;179414463
N2B	21597	65014;65015;65016	chr2:178549738;178549737;178549736	chr2:179414465;179414464;179414463
Novex-1	21722	65389;65390;65391	chr2:178549738;178549737;178549736	chr2:179414465;179414464;179414463
Novex-2	21789	65590;65591;65592	chr2:178549738;178549737;178549736	chr2:179414465;179414464;179414463
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: Fn3-111
• Domain position: 44
• Structural Position: 50
• Q(SASA): 0.425
• 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	rs2154148455	None	1.0	N	0.709	0.484	0.473774312618	gnomAD-4.0.0	3.18293E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71726E-06	0	0
T/P	None	None	1.0	N	0.647	0.565	0.449669948863	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	1.26695E-04	0	None	0	0	None	0	0	0	0	0
T/S	None	None	0.999	N	0.577	0.322	0.233785782151	gnomAD-4.0.0	1.59146E-06	None	None	None	None	N	None	0	0	None	4.76781E-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
T/A	0.3421	ambiguous	0.4922	ambiguous	-0.797	Destabilizing	0.999	D	0.556	neutral	N	0.520596387	None	None	N
T/C	0.8878	likely_pathogenic	0.9319	pathogenic	-0.548	Destabilizing	1.0	D	0.62	neutral	None	None	None	None	N
T/D	0.9051	likely_pathogenic	0.9326	pathogenic	-0.325	Destabilizing	1.0	D	0.69	prob.neutral	None	None	None	None	N
T/E	0.8872	likely_pathogenic	0.9264	pathogenic	-0.334	Destabilizing	1.0	D	0.696	prob.neutral	None	None	None	None	N
T/F	0.92	likely_pathogenic	0.9597	pathogenic	-0.804	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
T/G	0.7027	likely_pathogenic	0.7787	pathogenic	-1.049	Destabilizing	1.0	D	0.688	prob.neutral	None	None	None	None	N
T/H	0.8645	likely_pathogenic	0.9225	pathogenic	-1.259	Destabilizing	1.0	D	0.68	prob.neutral	None	None	None	None	N
T/I	0.7684	likely_pathogenic	0.8658	pathogenic	-0.218	Destabilizing	1.0	D	0.661	neutral	N	0.478054282	None	None	N
T/K	0.7273	likely_pathogenic	0.8215	pathogenic	-0.84	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	N
T/L	0.5045	ambiguous	0.6269	pathogenic	-0.218	Destabilizing	0.999	D	0.605	neutral	None	None	None	None	N
T/M	0.2996	likely_benign	0.4298	ambiguous	0.052	Stabilizing	1.0	D	0.627	neutral	None	None	None	None	N
T/N	0.5101	ambiguous	0.6223	pathogenic	-0.724	Destabilizing	1.0	D	0.709	prob.delet.	N	0.489094646	None	None	N
T/P	0.6415	likely_pathogenic	0.7742	pathogenic	-0.379	Destabilizing	1.0	D	0.647	neutral	N	0.472382743	None	None	N
T/Q	0.7766	likely_pathogenic	0.869	pathogenic	-0.927	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
T/R	0.7096	likely_pathogenic	0.8251	pathogenic	-0.527	Destabilizing	1.0	D	0.662	neutral	None	None	None	None	N
T/S	0.3439	ambiguous	0.4796	ambiguous	-1.002	Destabilizing	0.999	D	0.577	neutral	N	0.507301803	None	None	N
T/V	0.562	ambiguous	0.6843	pathogenic	-0.379	Destabilizing	0.999	D	0.613	neutral	None	None	None	None	N
T/W	0.9781	likely_pathogenic	0.9892	pathogenic	-0.715	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	N
T/Y	0.9181	likely_pathogenic	0.955	pathogenic	-0.513	Destabilizing	1.0	D	0.715	prob.delet.	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.