TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19741	59446;59447;59448	chr2:178592898;178592897;178592896	chr2:179457625;179457624;179457623
N2AB	18100	54523;54524;54525	chr2:178592898;178592897;178592896	chr2:179457625;179457624;179457623
N2A	17173	51742;51743;51744	chr2:178592898;178592897;178592896	chr2:179457625;179457624;179457623
N2B	10676	32251;32252;32253	chr2:178592898;178592897;178592896	chr2:179457625;179457624;179457623
Novex-1	10801	32626;32627;32628	chr2:178592898;178592897;178592896	chr2:179457625;179457624;179457623
Novex-2	10868	32827;32828;32829	chr2:178592898;178592897;178592896	chr2:179457625;179457624;179457623
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-31
• Domain position: 62
• Structural Position: 90
• Q(SASA): 0.5741
• 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
K/E	rs1283284446	None	0.012	N	0.446	0.147	0.178374595973	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
K/E	rs1283284446	None	0.012	N	0.446	0.147	0.178374595973	gnomAD-4.0.0	6.5773E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47106E-05	0	0
K/T	rs1443597990	None	None	N	0.321	0.203	0.156986980423	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	1.94326E-04	None	0	0	0	0	0
K/T	rs1443597990	None	None	N	0.321	0.203	0.156986980423	gnomAD-4.0.0	2.03017E-06	None	None	None	None	N	None	0	0	None	0	1.13947E-04	None	0	0	0	0	3.40275E-05

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
K/A	0.3135	likely_benign	0.1729	benign	-0.392	Destabilizing	0.016	N	0.443	neutral	None	None	None	None	N
K/C	0.5379	ambiguous	0.4269	ambiguous	-0.423	Destabilizing	0.864	D	0.593	neutral	None	None	None	None	N
K/D	0.6336	likely_pathogenic	0.4308	ambiguous	-0.058	Destabilizing	0.038	N	0.445	neutral	None	None	None	None	N
K/E	0.2137	likely_benign	0.1609	benign	0.043	Stabilizing	0.012	N	0.446	neutral	N	0.396189883	None	None	N
K/F	0.7061	likely_pathogenic	0.5352	ambiguous	-0.124	Destabilizing	0.356	N	0.591	neutral	None	None	None	None	N
K/G	0.4622	ambiguous	0.3223	benign	-0.718	Destabilizing	0.016	N	0.487	neutral	None	None	None	None	N
K/H	0.2201	likely_benign	0.161	benign	-0.89	Destabilizing	0.001	N	0.377	neutral	None	None	None	None	N
K/I	0.3183	likely_benign	0.2021	benign	0.436	Stabilizing	0.171	N	0.622	neutral	N	0.491390988	None	None	N
K/L	0.3957	ambiguous	0.248	benign	0.436	Stabilizing	0.038	N	0.51	neutral	None	None	None	None	N
K/M	0.2404	likely_benign	0.1478	benign	0.06	Stabilizing	0.356	N	0.581	neutral	None	None	None	None	N
K/N	0.363	ambiguous	0.1868	benign	-0.268	Destabilizing	None	N	0.224	neutral	N	0.462241517	None	None	N
K/P	0.9577	likely_pathogenic	0.845	pathogenic	0.19	Stabilizing	0.136	N	0.593	neutral	None	None	None	None	N
K/Q	0.1194	likely_benign	0.1004	benign	-0.28	Destabilizing	0.002	N	0.379	neutral	N	0.446002628	None	None	N
K/R	0.0715	likely_benign	0.0711	benign	-0.374	Destabilizing	0.055	N	0.392	neutral	N	0.449714937	None	None	N
K/S	0.3181	likely_benign	0.1762	benign	-0.804	Destabilizing	0.016	N	0.423	neutral	None	None	None	None	N
K/T	0.1239	likely_benign	0.0692	benign	-0.511	Destabilizing	None	N	0.321	neutral	N	0.4124847	None	None	N
K/V	0.2706	likely_benign	0.1877	benign	0.19	Stabilizing	0.038	N	0.528	neutral	None	None	None	None	N
K/W	0.7206	likely_pathogenic	0.6197	pathogenic	-0.086	Destabilizing	0.864	D	0.607	neutral	None	None	None	None	N
K/Y	0.5656	likely_pathogenic	0.4063	ambiguous	0.193	Stabilizing	0.214	N	0.616	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.