NM_000260.4(MYO7A):c.2489G>A (p.Arg830His) AND not provided

Germline classification:: Uncertain significance (3 submissions)
Last evaluated:: Sep 1, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000171199.8

Allele description [Variation Report for NM_000260.4(MYO7A):c.2489G>A (p.Arg830His)]

NM_000260.4(MYO7A):c.2489G>A (p.Arg830His)

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.2489G>A (p.Arg830His)

HGVS:

NC_000011.10:g.77179856G>A
NG_009086.2:g.56611G>A
NM_000260.4:c.2489G>AMANE SELECT
NM_001127180.2:c.2489G>A
NM_001369365.1:c.2456G>A
NP_000251.3:p.Arg830His
NP_001120652.1:p.Arg830His
NP_001356294.1:p.Arg819His
LRG_1420t1:c.2489G>A
LRG_1420:g.56611G>A
LRG_1420p1:p.Arg830His
NC_000011.9:g.76890902G>A
NG_009086.1:g.56593G>A
NM_000260.3:c.2489G>A

Protein change:

R819H

Links:

dbSNP: rs371029653

NCBI 1000 Genomes Browser:

rs371029653

Molecular consequence:

NM_000260.4:c.2489G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001127180.2:c.2489G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001369365.1:c.2456G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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Influenza A virus (A/New York/593/1996(H3N2)) segment 6, complete sequence
Influenza A virus (A/New York/593/1996(H3N2)) segment 6, complete sequence
gi|89789884|gnl|NIGSP|NIGSP-NYS-005 |gb|CY009910.1|

Nucleotide
Homo sapiens cDNA FLJ61638 complete cds, highly similar to Deleted in azoospermi...
Homo sapiens cDNA FLJ61638 complete cds, highly similar to Deleted in azoospermia protein 2
gi|221044035|dbj|AK302398.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001415477	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 1, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 27766948, 28492532
SCV001805670	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Dec 7, 2020)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001415477

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 1, 2022)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV001805670

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Dec 7, 2020)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing, research
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Utilization of amplicon-based targeted sequencing panel for the massively parallel sequencing of sporadic hearing impairment patients from Saudi Arabia.

Dallol A, Daghistani K, Elaimi A, Al-Wazani WA, Bamanie A, Safiah M, Sagaty S, Taha L, Zahed R, Bajouh O, Chaudhary AG, Gari MA, Turki R, Al-Qahtani MH, Abuzenadah AM.

BMC Med Genet. 2016 Oct 10;17(Suppl 1):67.

PubMed [citation]

PMID:: 27766948
PMCID:: PMC5073994

See all PubMed Citations (3)

Details of each submission

From Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center, SCV000221396.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	research	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Invitae, SCV001415477.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 830 of the MYO7A protein (p.Arg830His). This variant is present in population databases (rs371029653, gnomAD 0.02%). This missense change has been observed in individual(s) with autosomal recessive hearing loss (PMID: 27766948). ClinVar contains an entry for this variant (Variation ID: 191024). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MYO7A protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From GeneDx, SCV001805670.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 32884365, 27766948)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Flagged submissions

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000221396	Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	flagged submission Reason: This record appears to be redundant with a more recent record from the same submitter. Notes: SCV000221396 appears to be redundant with SCV004805726. (ACMG Guidelines, 2015)	Likely pathogenic	germline	research	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000221396

Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center

flagged submission

Reason: This record appears to be redundant with a more recent record from the same submitter.

Notes: SCV000221396 appears to be redundant with SCV004805726.

(ACMG Guidelines, 2015)

Likely pathogenic

germline

research

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

Last Updated: Aug 11, 2024

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Relating variation to medicine