NM_000260.4(MYO7A):c.3862G>C (p.Ala1288Pro) AND not provided

Germline classification:: Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:: Dec 24, 2023
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:: RCV001339495.10

Allele description [Variation Report for NM_000260.4(MYO7A):c.3862G>C (p.Ala1288Pro)]

NM_000260.4(MYO7A):c.3862G>C (p.Ala1288Pro)

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.3862G>C (p.Ala1288Pro)

Other names:

NM_000260.4(MYO7A):c.3862G>C; p.Ala1288Pro

HGVS:

NC_000011.10:g.77190808G>C
NG_009086.2:g.67563G>C
NM_000260.4:c.3862G>CMANE SELECT
NM_001127180.2:c.3862G>C
NM_001369365.1:c.3829G>C
NP_000251.3:p.Ala1288Pro
NP_001120652.1:p.Ala1288Pro
NP_001356294.1:p.Ala1277Pro
LRG_1420t1:c.3862G>C
LRG_1420:g.67563G>C
LRG_1420p1:p.Ala1288Pro
NC_000011.9:g.76901853G>C
NG_009086.1:g.67544G>C
NM_000260.3:c.3862G>C

Protein change:

A1277P

Links:

dbSNP: rs749747871

NCBI 1000 Genomes Browser:

rs749747871

Molecular consequence:

NM_000260.4:c.3862G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001127180.2:c.3862G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001369365.1:c.3829G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001533246	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 24, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 10094549, 10930322, 26969326, 28492532
SCV001762131	Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jun 17, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002017875	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Dec 17, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001533246

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 24, 2023)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

SCV001762131

Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Jun 17, 2021)

germline

clinical testing

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

SCV002017875

Revvity Omics, Revvity

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Dec 17, 2019)

germline

clinical testing

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

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	1	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Twelve novel myosin VIIA mutations in 34 patients with Usher syndrome type I: confirmation of genetic heterogeneity.

Janecke AR, Meins M, Sadeghi M, Grundmann K, Apfelstedt-Sylla E, Zrenner E, Rosenberg T, Gal A.

Hum Mutat. 1999;13(2):133-40.

PubMed [citation]

PMID:: 10094549

Evaluation of the myosin VIIA gene and visual function in patients with Usher syndrome type I.

Bharadwaj AK, Kasztejna JP, Huq S, Berson EL, Dryja TP.

Exp Eye Res. 2000 Aug;71(2):173-81.

PubMed [citation]

PMID:: 10930322

See all PubMed Citations (5)

Details of each submission

From Invitae, SCV001533246.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 1288 of the MYO7A protein (p.Ala1288Pro). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with Usher syndrome (PMID: 10094549, 10930322, 26969326; Invitae). ClinVar contains an entry for this variant (Variation ID: 866837). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on MYO7A protein function. For these reasons, this variant has been classified as Pathogenic.

#	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 Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen, SCV001762131.1

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

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

From Revvity Omics, Revvity, SCV002017875.3

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

#	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

Last Updated: May 7, 2024

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