TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35738	107437;107438;107439	chr2:178528539;178528538;178528537	chr2:179393266;179393265;179393264
N2AB	34097	102514;102515;102516	chr2:178528539;178528538;178528537	chr2:179393266;179393265;179393264
N2A	33170	99733;99734;99735	chr2:178528539;178528538;178528537	chr2:179393266;179393265;179393264
N2B	26673	80242;80243;80244	chr2:178528539;178528538;178528537	chr2:179393266;179393265;179393264
Novex-1	26798	80617;80618;80619	chr2:178528539;178528538;178528537	chr2:179393266;179393265;179393264
Novex-2	26865	80818;80819;80820	chr2:178528539;178528538;178528537	chr2:179393266;179393265;179393264
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: Ig-168
• Domain position: 37
• Structural Position: 51
• Q(SASA): 0.7772
• 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/K	None	None	0.117	N	0.322	0.132	0.115124310173	gnomAD-4.0.0	1.60895E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.89233E-06	0	0
N/S	rs774996138	0.26	0.027	N	0.385	0.157	0.112648838833	gnomAD-2.1.1	1.23E-05	None	None	None	None	N	None	0	0	None	0	0	None	1.001E-04	None	0	0	0
N/S	rs774996138	0.26	0.027	N	0.385	0.157	0.112648838833	gnomAD-4.0.0	8.24405E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.40236E-04	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	0.7234	likely_pathogenic	0.7071	pathogenic	-0.716	Destabilizing	0.149	N	0.411	neutral	None	None	None	None	N
N/C	0.807	likely_pathogenic	0.8132	pathogenic	0.206	Stabilizing	0.935	D	0.422	neutral	None	None	None	None	N
N/D	0.1415	likely_benign	0.1268	benign	0.117	Stabilizing	None	N	0.167	neutral	N	0.375342103	None	None	N
N/E	0.6524	likely_pathogenic	0.6171	pathogenic	0.147	Stabilizing	0.035	N	0.333	neutral	None	None	None	None	N
N/F	0.9472	likely_pathogenic	0.9339	pathogenic	-0.76	Destabilizing	0.791	D	0.413	neutral	None	None	None	None	N
N/G	0.533	ambiguous	0.5032	ambiguous	-0.979	Destabilizing	0.067	N	0.364	neutral	None	None	None	None	N
N/H	0.4056	ambiguous	0.3745	ambiguous	-0.834	Destabilizing	0.484	N	0.331	neutral	N	0.505680076	None	None	N
N/I	0.8673	likely_pathogenic	0.8594	pathogenic	-0.082	Destabilizing	0.484	N	0.423	neutral	N	0.463448157	None	None	N
N/K	0.7534	likely_pathogenic	0.7154	pathogenic	-0.097	Destabilizing	0.117	N	0.322	neutral	N	0.489190471	None	None	N
N/L	0.8122	likely_pathogenic	0.7929	pathogenic	-0.082	Destabilizing	0.262	N	0.43	neutral	None	None	None	None	N
N/M	0.8261	likely_pathogenic	0.8101	pathogenic	0.309	Stabilizing	0.935	D	0.407	neutral	None	None	None	None	N
N/P	0.9894	likely_pathogenic	0.9895	pathogenic	-0.264	Destabilizing	0.555	D	0.399	neutral	None	None	None	None	N
N/Q	0.7242	likely_pathogenic	0.6886	pathogenic	-0.53	Destabilizing	0.149	N	0.337	neutral	None	None	None	None	N
N/R	0.8071	likely_pathogenic	0.7737	pathogenic	-0.104	Destabilizing	0.38	N	0.331	neutral	None	None	None	None	N
N/S	0.2351	likely_benign	0.2312	benign	-0.501	Destabilizing	0.027	N	0.385	neutral	N	0.483437935	None	None	N
N/T	0.6299	likely_pathogenic	0.6298	pathogenic	-0.291	Destabilizing	0.117	N	0.333	neutral	N	0.459155743	None	None	N
N/V	0.8561	likely_pathogenic	0.8519	pathogenic	-0.264	Destabilizing	0.555	D	0.412	neutral	None	None	None	None	N
N/W	0.9665	likely_pathogenic	0.9613	pathogenic	-0.603	Destabilizing	0.935	D	0.525	neutral	None	None	None	None	N
N/Y	0.5074	ambiguous	0.4744	ambiguous	-0.401	Destabilizing	0.741	D	0.405	neutral	N	0.474804463	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.