TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13805	41638;41639;41640	chr2:178636158;178636157;178636156	chr2:179500885;179500884;179500883
N2AB	12164	36715;36716;36717	chr2:178636158;178636157;178636156	chr2:179500885;179500884;179500883
N2A	11237	33934;33935;33936	chr2:178636158;178636157;178636156	chr2:179500885;179500884;179500883
N2B	4740	14443;14444;14445	chr2:178636158;178636157;178636156	chr2:179500885;179500884;179500883
Novex-1	4865	14818;14819;14820	chr2:178636158;178636157;178636156	chr2:179500885;179500884;179500883
Novex-2	4932	15019;15020;15021	chr2:178636158;178636157;178636156	chr2:179500885;179500884;179500883
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-88
• Domain position: 26
• Structural Position: 38
• Q(SASA): 0.574
• 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	rs753262730	-0.071	0.961	N	0.488	0.139	0.0846915920261	gnomAD-2.1.1	8.07E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
N/K	rs753262730	-0.071	0.961	N	0.488	0.139	0.0846915920261	gnomAD-4.0.0	1.5932E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86102E-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	0.8535	likely_pathogenic	0.8724	pathogenic	-0.374	Destabilizing	0.871	D	0.552	neutral	None	None	None	None	N
N/C	0.8753	likely_pathogenic	0.8816	pathogenic	0.158	Stabilizing	1.0	D	0.776	deleterious	None	None	None	None	N
N/D	0.5526	ambiguous	0.6123	pathogenic	0.302	Stabilizing	0.961	D	0.475	neutral	N	0.345736523	None	None	N
N/E	0.9468	likely_pathogenic	0.9598	pathogenic	0.335	Stabilizing	0.97	D	0.441	neutral	None	None	None	None	N
N/F	0.9754	likely_pathogenic	0.9763	pathogenic	-0.423	Destabilizing	0.999	D	0.765	deleterious	None	None	None	None	N
N/G	0.8252	likely_pathogenic	0.8506	pathogenic	-0.629	Destabilizing	0.931	D	0.469	neutral	None	None	None	None	N
N/H	0.7056	likely_pathogenic	0.7175	pathogenic	-0.414	Destabilizing	0.998	D	0.553	neutral	N	0.318029298	None	None	N
N/I	0.8874	likely_pathogenic	0.8983	pathogenic	0.228	Stabilizing	0.989	D	0.769	deleterious	N	0.333564531	None	None	N
N/K	0.9827	likely_pathogenic	0.9866	pathogenic	0.065	Stabilizing	0.961	D	0.488	neutral	N	0.342422716	None	None	N
N/L	0.8515	likely_pathogenic	0.8532	pathogenic	0.228	Stabilizing	0.97	D	0.593	neutral	None	None	None	None	N
N/M	0.9091	likely_pathogenic	0.9157	pathogenic	0.304	Stabilizing	1.0	D	0.722	deleterious	None	None	None	None	N
N/P	0.9729	likely_pathogenic	0.9722	pathogenic	0.057	Stabilizing	0.996	D	0.7	prob.delet.	None	None	None	None	N
N/Q	0.9441	likely_pathogenic	0.9488	pathogenic	-0.395	Destabilizing	0.996	D	0.511	neutral	None	None	None	None	N
N/R	0.9728	likely_pathogenic	0.9766	pathogenic	0.059	Stabilizing	0.996	D	0.502	neutral	None	None	None	None	N
N/S	0.1334	likely_benign	0.1473	benign	-0.384	Destabilizing	0.287	N	0.269	neutral	N	0.316899383	None	None	N
N/T	0.4489	ambiguous	0.5023	ambiguous	-0.177	Destabilizing	0.248	N	0.334	neutral	N	0.346334403	None	None	N
N/V	0.8683	likely_pathogenic	0.8842	pathogenic	0.057	Stabilizing	0.991	D	0.593	neutral	None	None	None	None	N
N/W	0.989	likely_pathogenic	0.9881	pathogenic	-0.323	Destabilizing	1.0	D	0.721	deleterious	None	None	None	None	N
N/Y	0.8089	likely_pathogenic	0.803	pathogenic	-0.067	Destabilizing	0.998	D	0.747	deleterious	N	0.334720111	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.