TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27500	82723;82724;82725	chr2:178563634;178563633;178563632	chr2:179428361;179428360;179428359
N2AB	25859	77800;77801;77802	chr2:178563634;178563633;178563632	chr2:179428361;179428360;179428359
N2A	24932	75019;75020;75021	chr2:178563634;178563633;178563632	chr2:179428361;179428360;179428359
N2B	18435	55528;55529;55530	chr2:178563634;178563633;178563632	chr2:179428361;179428360;179428359
Novex-1	18560	55903;55904;55905	chr2:178563634;178563633;178563632	chr2:179428361;179428360;179428359
Novex-2	18627	56104;56105;56106	chr2:178563634;178563633;178563632	chr2:179428361;179428360;179428359
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-88
• Domain position: 32
• Structural Position: 34
• Q(SASA): 0.7213
• Predicted PPI site: I

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
E/A	None	None	0.001	N	0.281	0.246	0.226586394389	gnomAD-4.0.0	1.59122E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	2.4108E-04	0	0	0
E/K	rs375422359	0.742	0.574	N	0.487	0.164	None	gnomAD-2.1.1	2.41E-05	None	None	None	None	I	None	6.46E-05	8.69E-05	None	0	5.57E-05	None	3.27E-05	None	0	0	0
E/K	rs375422359	0.742	0.574	N	0.487	0.164	None	gnomAD-3.1.2	3.29E-05	None	None	None	None	I	None	9.66E-05	0	0	0	0	None	0	0	1.47E-05	0	0
E/K	rs375422359	0.742	0.574	N	0.487	0.164	None	gnomAD-4.0.0	1.1155E-05	None	None	None	None	I	None	1.06843E-04	5.00233E-05	None	0	2.22946E-05	None	0	0	2.54286E-06	3.29352E-05	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
E/A	0.1086	likely_benign	0.1096	benign	-0.24	Destabilizing	0.001	N	0.281	neutral	N	0.475634889	None	None	I
E/C	0.7542	likely_pathogenic	0.7468	pathogenic	0.013	Stabilizing	0.944	D	0.536	neutral	None	None	None	None	I
E/D	0.0906	likely_benign	0.0914	benign	-0.25	Destabilizing	0.001	N	0.237	neutral	N	0.489121474	None	None	I
E/F	0.7236	likely_pathogenic	0.7172	pathogenic	-0.189	Destabilizing	0.818	D	0.518	neutral	None	None	None	None	I
E/G	0.1348	likely_benign	0.1461	benign	-0.421	Destabilizing	0.193	N	0.557	neutral	N	0.477462079	None	None	I
E/H	0.3757	ambiguous	0.3975	ambiguous	0.099	Stabilizing	0.818	D	0.436	neutral	None	None	None	None	I
E/I	0.3248	likely_benign	0.3016	benign	0.194	Stabilizing	0.69	D	0.539	neutral	None	None	None	None	I
E/K	0.1163	likely_benign	0.1198	benign	0.398	Stabilizing	0.574	D	0.487	neutral	N	0.502050699	None	None	I
E/L	0.353	ambiguous	0.3541	ambiguous	0.194	Stabilizing	0.241	N	0.506	neutral	None	None	None	None	I
E/M	0.389	ambiguous	0.3859	ambiguous	0.217	Stabilizing	0.944	D	0.522	neutral	None	None	None	None	I
E/N	0.1717	likely_benign	0.1785	benign	0.163	Stabilizing	0.388	N	0.443	neutral	None	None	None	None	I
E/P	0.2257	likely_benign	0.2397	benign	0.07	Stabilizing	0.005	N	0.294	neutral	None	None	None	None	I
E/Q	0.1195	likely_benign	0.128	benign	0.182	Stabilizing	0.016	N	0.264	neutral	N	0.509747462	None	None	I
E/R	0.195	likely_benign	0.2074	benign	0.596	Stabilizing	0.527	D	0.429	neutral	None	None	None	None	I
E/S	0.1487	likely_benign	0.1575	benign	-0.018	Destabilizing	0.241	N	0.442	neutral	None	None	None	None	I
E/T	0.1805	likely_benign	0.1836	benign	0.127	Stabilizing	0.388	N	0.528	neutral	None	None	None	None	I
E/V	0.184	likely_benign	0.1709	benign	0.07	Stabilizing	0.193	N	0.507	neutral	N	0.492501687	None	None	I
E/W	0.8646	likely_pathogenic	0.8722	pathogenic	-0.076	Destabilizing	0.981	D	0.636	neutral	None	None	None	None	I
E/Y	0.5685	likely_pathogenic	0.5671	pathogenic	0.052	Stabilizing	0.818	D	0.538	neutral	None	None	None	None	I

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.