UniProtKB/Swiss-Prot Q96KG7: Variant p.Cys774Arg

Multiple epidermal growth factor-like domains protein 10
Gene: MEGF10
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Variant information Variant position:

774 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

LP/P [Disclaimer] The variants are classified into three categories: LP/P, LB/B and US.

LP/P: likely pathogenic or pathogenic.
LB/B: likely benign or benign.
US: uncertain significance

Residue change:

From Cysteine (C) to Arginine (R) at position 774 (C774R, p.Cys774Arg). Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.
Physico-chemical properties:

Change from medium size and polar (C) to large size and basic (R) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

-3 The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:

Lowest score: -4 (low probability of substitution).
Highest score: 11 (high probability of substitution).

More information can be found on the following page
Variant description:

In CMYP10B and CMYP10A; impaired tyrosine phosphorylation; no effect on cell membrane location; impairs binding to C1q; reduced apoptotic cell engulfement by astrocytes by 50%; reduced myoblast migration and proliferation; decreased interaction with NOTCH1; no effect on NOTCH1 nuclear location. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs387907072 [ dbSNP | Ensembl ]

Sequence information Variant position:

774 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

1140 The length of the canonical sequence.
Location on the sequence:

DCALICQCQNGADCDHISGQ C TCRTGFMGRHCEQKCPSGTY The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.
Residue conservation:

The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         DCALICQCQNGADCDHISGQCTCRTGFMGRHCEQKCPSGTY

Mouse                         DCALICQCQNGADCDHISGQCTCRTGFMGRHCEQKCPAGTY

Xenopus tropicalis            ECTLVCQCQNGADCDHITGQCTCRTGFMGKFCEQKCPSASY

Zebrafish                     DCVQACQCENGADCNHISGQCTCRTGFMGRHCETKCPAGSY

Sequence annotation in neighborhood:

The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:

Type: the type of sequence feature.
Positions: endpoints of the sequence feature.
Description: contains additional information about the feature.

Type	Positions	Description
Chain	26 – 1140	Multiple epidermal growth factor-like domains protein 10
Topological domain	26 – 857	Extracellular
Domain	751 – 786	EGF-like 14
Region	1 – 857	Necessary for interaction with AP2M1, self-assembly and formation of the irregular, mosaic-like adhesion pattern
Disulfide bond	761 – 774
Alternative sequence	568 – 1140	Missing. In isoform 2.

Literature citations
Mutations in MEGF10, a regulator of satellite cell myogenesis, cause early onset myopathy, areflexia, respiratory distress and dysphagia (EMARDD).
Logan C.V.; Lucke B.; Pottinger C.; Abdelhamed Z.A.; Parry D.A.; Szymanska K.; Diggle C.P.; Riesen A.; Morgan J.E.; Markham G.; Ellis I.; Manzur A.Y.; Markham A.F.; Shires M.; Helliwell T.; Scoto M.; Hubner C.; Bonthron D.T.; Taylor G.R.; Sheridan E.; Muntoni F.; Carr I.M.; Schuelke M.; Johnson C.A.;
Nat. Genet. 43:1189-1192(2011)
Cited for: FUNCTION IN MYOGENESIS; VARIANT CMYP10A ARG-774; Mutations in the satellite cell gene MEGF10 cause a recessive congenital myopathy with minicores.
Boyden S.E.; Mahoney L.J.; Kawahara G.; Myers J.A.; Mitsuhashi S.; Estrella E.A.; Duncan A.R.; Dey F.; Dechene E.T.; Blasko-Goehringer J.M.; Bonnemann C.G.; Darras B.T.; Mendell J.R.; Lidov H.G.; Nishino I.; Beggs A.H.; Kunkel L.M.; Kang P.B.;
Neurogenetics 13:115-124(2012)
Cited for: INVOLVEMENT IN CMYP10B; VARIANTS CMYP10B TRP-71; ARG-326 AND ARG-774; Cysteine mutations cause defective tyrosine phosphorylation in MEGF10 myopathy.
Mitsuhashi S.; Mitsuhashi H.; Alexander M.S.; Sugimoto H.; Kang P.B.;
FEBS Lett. 587:2952-2957(2013)
Cited for: CHARACTERIZATION OF VARIANT CMYP10B ARG-326; CHARACTERIZATION OF VARIANT CMYP10A/CMYP10B ARG-774; MUTAGENESIS OF TYR-1030; PHOSPHORYLATION AT TYR-1030; Megf10 Is a Receptor for C1Q That Mediates Clearance of Apoptotic Cells by Astrocytes.
Iram T.; Ramirez-Ortiz Z.; Byrne M.H.; Coleman U.A.; Kingery N.D.; Means T.K.; Frenkel D.; El Khoury J.;
J. Neurosci. 36:5185-5192(2016)
Cited for: CHARACTERIZATION OF VARIANT CMYP10B ARG-326; CHARACTERIZATION OF VARIANT CMYP10A/CMYP10B ARG-774; FUNCTION; INTERACTION WITH COMPLEMENT C1Q; SUBCELLULAR LOCATION; Japanese multiple epidermal growth factor 10 (MEGF10) myopathy with novel mutations: A phenotype-genotype correlation.
Takayama K.; Mitsuhashi S.; Shin J.Y.; Tanaka R.; Fujii T.; Tsuburaya R.; Mukaida S.; Noguchi S.; Nonaka I.; Nishino I.;
Neuromuscul. Disord. 26:604-609(2016)
Cited for: INVOLVEMENT IN CMYP10B; INVOLVEMENT IN CMYP10A; TISSUE SPECIFICITY; VARIANT CMYP10B TYR-810; CHARACTERIZATION OF VARIANTS CMYP10B ARG-326; ARG-774 AND TYR-810; Consequences of MEGF10 deficiency on myoblast function and Notch1 interactions.
Saha M.; Mitsuhashi S.; Jones M.D.; Manko K.; Reddy H.M.; Bruels C.; Cho K.A.; Pacak C.A.; Draper I.; Kang P.B.;
Hum. Mol. Genet. 26:2984-3000(2017)
Cited for: CHARACTERIZATION OF VARIANT CMYP10B ARG-326; CHARACTERIZATION OF VARIANT CMYP10A/CMYP10B ARG-774; FUNCTION; INTERACTION WITH NOTCH1; Selective serotonin reuptake inhibitors ameliorate MEGF10 myopathy.
Saha M.; Rizzo S.A.; Ramanathan M.; Hightower R.M.; Santostefano K.E.; Terada N.; Finkel R.S.; Berg J.S.; Chahin N.; Pacak C.A.; Wagner R.E.; Alexander M.S.; Draper I.; Kang P.B.;
Cited for: VARIANT CMYP10A ARG-774; VARIANT CYS-1030; FUNCTION;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.