TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22322	67189;67190;67191	chr2:178580415;178580414;178580413	chr2:179445142;179445141;179445140
N2AB	20681	62266;62267;62268	chr2:178580415;178580414;178580413	chr2:179445142;179445141;179445140
N2A	19754	59485;59486;59487	chr2:178580415;178580414;178580413	chr2:179445142;179445141;179445140
N2B	13257	39994;39995;39996	chr2:178580415;178580414;178580413	chr2:179445142;179445141;179445140
Novex-1	13382	40369;40370;40371	chr2:178580415;178580414;178580413	chr2:179445142;179445141;179445140
Novex-2	13449	40570;40571;40572	chr2:178580415;178580414;178580413	chr2:179445142;179445141;179445140
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: Ig-126
• Domain position: 58
• Structural Position: 141
• Q(SASA): 0.6428
• 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
E/G	None	None	0.988	N	0.525	0.463	0.443285836454	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31251E-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
E/A	0.3248	likely_benign	0.3382	benign	-0.336	Destabilizing	0.958	D	0.53	neutral	N	0.517474016	None	None	N
E/C	0.92	likely_pathogenic	0.9249	pathogenic	0.272	Stabilizing	1.0	D	0.633	neutral	None	None	None	None	N
E/D	0.1415	likely_benign	0.1422	benign	-0.448	Destabilizing	0.979	D	0.43	neutral	N	0.475646036	None	None	N
E/F	0.9137	likely_pathogenic	0.9231	pathogenic	-0.552	Destabilizing	1.0	D	0.616	neutral	None	None	None	None	N
E/G	0.2667	likely_benign	0.2962	benign	-0.538	Destabilizing	0.988	D	0.525	neutral	N	0.489126278	None	None	N
E/H	0.701	likely_pathogenic	0.7206	pathogenic	-0.686	Destabilizing	1.0	D	0.535	neutral	None	None	None	None	N
E/I	0.643	likely_pathogenic	0.6626	pathogenic	0.159	Stabilizing	0.995	D	0.651	neutral	None	None	None	None	N
E/K	0.3094	likely_benign	0.3493	ambiguous	0.37	Stabilizing	0.958	D	0.503	neutral	N	0.475125961	None	None	N
E/L	0.6683	likely_pathogenic	0.6853	pathogenic	0.159	Stabilizing	0.991	D	0.633	neutral	None	None	None	None	N
E/M	0.7386	likely_pathogenic	0.7525	pathogenic	0.536	Stabilizing	1.0	D	0.557	neutral	None	None	None	None	N
E/N	0.3669	ambiguous	0.3785	ambiguous	0.193	Stabilizing	0.995	D	0.574	neutral	None	None	None	None	N
E/P	0.5672	likely_pathogenic	0.579	pathogenic	0.015	Stabilizing	0.086	N	0.351	neutral	None	None	None	None	N
E/Q	0.2503	likely_benign	0.2616	benign	0.191	Stabilizing	0.994	D	0.513	neutral	N	0.521647685	None	None	N
E/R	0.4606	ambiguous	0.4938	ambiguous	0.332	Stabilizing	0.995	D	0.583	neutral	None	None	None	None	N
E/S	0.3222	likely_benign	0.3394	benign	0.01	Stabilizing	0.968	D	0.532	neutral	None	None	None	None	N
E/T	0.389	ambiguous	0.4103	ambiguous	0.17	Stabilizing	0.991	D	0.567	neutral	None	None	None	None	N
E/V	0.4387	ambiguous	0.4529	ambiguous	0.015	Stabilizing	0.994	D	0.567	neutral	N	0.521207755	None	None	N
E/W	0.9598	likely_pathogenic	0.9644	pathogenic	-0.514	Destabilizing	1.0	D	0.633	neutral	None	None	None	None	N
E/Y	0.8333	likely_pathogenic	0.8447	pathogenic	-0.323	Destabilizing	0.998	D	0.583	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.