TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14534	43825;43826;43827	chr2:178632294;178632293;178632292	chr2:179497021;179497020;179497019
N2AB	12893	38902;38903;38904	chr2:178632294;178632293;178632292	chr2:179497021;179497020;179497019
N2A	11966	36121;36122;36123	chr2:178632294;178632293;178632292	chr2:179497021;179497020;179497019
N2B	5469	16630;16631;16632	chr2:178632294;178632293;178632292	chr2:179497021;179497020;179497019
Novex-1	5594	17005;17006;17007	chr2:178632294;178632293;178632292	chr2:179497021;179497020;179497019
Novex-2	5661	17206;17207;17208	chr2:178632294;178632293;178632292	chr2:179497021;179497020;179497019
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAG
• RefSeq wild type template codon: GTC
• Domain: Ig-96
• Domain position: 38
• Structural Position: 55
• Q(SASA): 0.6075
• 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
Q/R	rs1431389358	0.109	0.096	N	0.258	0.204	0.249502417897	gnomAD-2.1.1	4.13E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.13E-06	0
Q/R	rs1431389358	0.109	0.096	N	0.258	0.204	0.249502417897	gnomAD-4.0.0	1.3722E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.80188E-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
Q/A	0.3469	ambiguous	0.2993	benign	-0.358	Destabilizing	0.002	N	0.184	neutral	None	None	None	None	N
Q/C	0.7505	likely_pathogenic	0.6394	pathogenic	0.121	Stabilizing	0.958	D	0.273	neutral	None	None	None	None	N
Q/D	0.4875	ambiguous	0.4204	ambiguous	0.046	Stabilizing	0.22	N	0.217	neutral	None	None	None	None	N
Q/E	0.1004	likely_benign	0.0899	benign	0.065	Stabilizing	0.042	N	0.273	neutral	N	0.499443068	None	None	N
Q/F	0.7556	likely_pathogenic	0.6745	pathogenic	-0.339	Destabilizing	0.667	D	0.315	neutral	None	None	None	None	N
Q/G	0.4329	ambiguous	0.3756	ambiguous	-0.614	Destabilizing	0.104	N	0.332	neutral	None	None	None	None	N
Q/H	0.275	likely_benign	0.2233	benign	-0.395	Destabilizing	0.602	D	0.277	neutral	N	0.515492695	None	None	N
Q/I	0.3547	ambiguous	0.3039	benign	0.247	Stabilizing	0.124	N	0.359	neutral	None	None	None	None	N
Q/K	0.0796	likely_benign	0.073	benign	-0.101	Destabilizing	None	N	0.171	neutral	N	0.459462273	None	None	N
Q/L	0.1907	likely_benign	0.1651	benign	0.247	Stabilizing	0.042	N	0.329	neutral	N	0.513494766	None	None	N
Q/M	0.3869	ambiguous	0.3553	ambiguous	0.437	Stabilizing	0.667	D	0.257	neutral	None	None	None	None	N
Q/N	0.3608	ambiguous	0.3146	benign	-0.479	Destabilizing	0.22	N	0.259	neutral	None	None	None	None	N
Q/P	0.7004	likely_pathogenic	0.6853	pathogenic	0.075	Stabilizing	0.301	N	0.357	neutral	D	0.539814176	None	None	N
Q/R	0.1116	likely_benign	0.0979	benign	0.043	Stabilizing	0.096	N	0.258	neutral	N	0.513236722	None	None	N
Q/S	0.3751	ambiguous	0.3275	benign	-0.513	Destabilizing	0.055	N	0.275	neutral	None	None	None	None	N
Q/T	0.2578	likely_benign	0.2206	benign	-0.321	Destabilizing	0.104	N	0.326	neutral	None	None	None	None	N
Q/V	0.269	likely_benign	0.2336	benign	0.075	Stabilizing	0.002	N	0.203	neutral	None	None	None	None	N
Q/W	0.6533	likely_pathogenic	0.5638	ambiguous	-0.287	Destabilizing	0.958	D	0.286	neutral	None	None	None	None	N
Q/Y	0.5652	likely_pathogenic	0.4687	ambiguous	-0.06	Destabilizing	0.859	D	0.317	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.