NM_000260.4(MYO7A):c.4757A>G (p.Asn1586Ser) AND not provided

Clinical significance:Conflicting interpretations of pathogenicity, Likely benign(1);Uncertain significance(2) (Last evaluated: Dec 6, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
3 submissions [Details]
Record status:
current
Accession:
RCV000724089.5

Allele description [Variation Report for NM_000260.4(MYO7A):c.4757A>G (p.Asn1586Ser)]

NM_000260.4(MYO7A):c.4757A>G (p.Asn1586Ser)

Gene:
MYO7A:myosin VIIA [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
11q13.5
Genomic location:
Preferred name:
NM_000260.4(MYO7A):c.4757A>G (p.Asn1586Ser)
HGVS:
  • NC_000011.10:g.77199723A>G
  • NG_009086.1:g.76459A>G
  • NG_009086.2:g.76478A>G
  • NM_000260.4:c.4757A>GMANE SELECT
  • NM_001127180.2:c.4643A>G
  • NM_001369365.1:c.4610A>G
  • NP_000251.3:p.Asn1586Ser
  • NP_001120652.1:p.Asn1548Ser
  • NP_001356294.1:p.Asn1537Ser
  • LRG_1420t1:c.4757A>G
  • LRG_1420:g.76478A>G
  • LRG_1420p1:p.Asn1586Ser
  • NC_000011.9:g.76910768A>G
  • NM_000260.3:c.4757A>G
Protein change:
N1537S
Links:
dbSNP: rs201251963
NCBI 1000 Genomes Browser:
rs201251963
Molecular consequence:
  • NM_000260.4:c.4757A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127180.2:c.4643A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369365.1:c.4610A>G - missense variant - [Sequence Ontology: SO:0001583]
Observations:
3

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000229762EGL Genetic Diagnostics, Eurofins Clinical Diagnosticscriteria provided, single submitter
Uncertain significance
(Feb 4, 2016)
germlineclinical testing

Citation Link,

SCV000582556GeneDxcriteria provided, single submitter
Uncertain significance
(May 15, 2017)
germlineclinical testing

Citation Link,

SCV001048924Invitaecriteria provided, single submitter
Likely benign
(Dec 6, 2020)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknown3not providednot providednot providednot providedclinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From EGL Genetic Diagnostics, Eurofins Clinical Diagnostics, SCV000229762.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided3not providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot provided3not providednot providednot provided

From GeneDx, SCV000582556.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The N1586S variant in the MYO7A gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The N1586S variant is observed in 35/8566 (0.41%) alleles from individuals of East Asian background, including 1 homozygous individual, in the ExAC dataset (Lek et al., 2016). The N1586S variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret N1586S as a variant of uncertain significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV001048924.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 18, 2021

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