TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22689	68290;68291;68292	chr2:178578965;178578964;178578963	chr2:179443692;179443691;179443690
N2AB	21048	63367;63368;63369	chr2:178578965;178578964;178578963	chr2:179443692;179443691;179443690
N2A	20121	60586;60587;60588	chr2:178578965;178578964;178578963	chr2:179443692;179443691;179443690
N2B	13624	41095;41096;41097	chr2:178578965;178578964;178578963	chr2:179443692;179443691;179443690
Novex-1	13749	41470;41471;41472	chr2:178578965;178578964;178578963	chr2:179443692;179443691;179443690
Novex-2	13816	41671;41672;41673	chr2:178578965;178578964;178578963	chr2:179443692;179443691;179443690
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Fn3-52
• Domain position: 47
• Structural Position: 63
• Q(SASA): 0.5666
• 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
N/D	rs786205382	None	0.822	N	0.325	0.288	0.216624796971	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-06	0	0
N/I	None	None	0.97	D	0.549	0.489	0.503990602145	gnomAD-4.0.0	6.84412E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.15942E-05	0
N/S	rs375397094	-0.832	0.822	N	0.331	0.218	None	gnomAD-4.0.0	2.05324E-06	None	None	None	None	N	None	2.99025E-05	0	None	0	0	None	0	0	1.79933E-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
N/A	0.3407	ambiguous	0.3124	benign	-0.518	Destabilizing	0.754	D	0.383	neutral	None	None	None	None	N
N/C	0.3069	likely_benign	0.2916	benign	0.355	Stabilizing	0.998	D	0.629	neutral	None	None	None	None	N
N/D	0.2113	likely_benign	0.1963	benign	-0.282	Destabilizing	0.822	D	0.325	neutral	N	0.433710908	None	None	N
N/E	0.5412	ambiguous	0.5213	ambiguous	-0.298	Destabilizing	0.754	D	0.284	neutral	None	None	None	None	N
N/F	0.7196	likely_pathogenic	0.6905	pathogenic	-0.753	Destabilizing	0.978	D	0.547	neutral	None	None	None	None	N
N/G	0.2439	likely_benign	0.2228	benign	-0.733	Destabilizing	0.86	D	0.293	neutral	None	None	None	None	N
N/H	0.1433	likely_benign	0.131	benign	-0.794	Destabilizing	0.032	N	0.23	neutral	D	0.522137969	None	None	N
N/I	0.5211	ambiguous	0.4574	ambiguous	-0.024	Destabilizing	0.97	D	0.549	neutral	D	0.526004994	None	None	N
N/K	0.4307	ambiguous	0.391	ambiguous	-0.118	Destabilizing	0.014	N	0.257	neutral	N	0.470823715	None	None	N
N/L	0.3439	ambiguous	0.322	benign	-0.024	Destabilizing	0.956	D	0.498	neutral	None	None	None	None	N
N/M	0.4674	ambiguous	0.4334	ambiguous	0.511	Stabilizing	0.998	D	0.499	neutral	None	None	None	None	N
N/P	0.7338	likely_pathogenic	0.651	pathogenic	-0.161	Destabilizing	0.978	D	0.459	neutral	None	None	None	None	N
N/Q	0.3623	ambiguous	0.3491	ambiguous	-0.595	Destabilizing	0.956	D	0.267	neutral	None	None	None	None	N
N/R	0.4456	ambiguous	0.4087	ambiguous	-0.044	Destabilizing	0.754	D	0.241	neutral	None	None	None	None	N
N/S	0.0999	likely_benign	0.0943	benign	-0.333	Destabilizing	0.822	D	0.331	neutral	N	0.468764844	None	None	N
N/T	0.2415	likely_benign	0.2102	benign	-0.2	Destabilizing	0.822	D	0.247	neutral	N	0.48142471	None	None	N
N/V	0.4628	ambiguous	0.4151	ambiguous	-0.161	Destabilizing	0.956	D	0.55	neutral	None	None	None	None	N
N/W	0.8307	likely_pathogenic	0.809	pathogenic	-0.673	Destabilizing	0.998	D	0.655	neutral	None	None	None	None	N
N/Y	0.2662	likely_benign	0.2477	benign	-0.446	Destabilizing	0.942	D	0.457	neutral	N	0.518020229	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.