NM_002473.6(MYH9):c.3673G>A (p.Glu1225Lys) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jan 1, 2024
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:: RCV002224634.2

Allele description [Variation Report for NM_002473.6(MYH9):c.3673G>A (p.Glu1225Lys)]

NM_002473.6(MYH9):c.3673G>A (p.Glu1225Lys)

Gene:

MYH9:myosin heavy chain 9 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

22q12.3

Genomic location:

Preferred name:

NM_002473.6(MYH9):c.3673G>A (p.Glu1225Lys)

HGVS:

NC_000022.11:g.36294256C>T
NG_011884.2:g.98763G>A
NM_002473.6:c.3673G>AMANE SELECT
NP_002464.1:p.Glu1225Lys
LRG_567:g.98763G>A
NC_000022.10:g.36690302C>T

Protein change:

E1225K

Links:

dbSNP: rs770864107

NCBI 1000 Genomes Browser:

rs770864107

Molecular consequence:

NM_002473.6:c.3673G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002502246	AiLife Diagnostics, AiLife Diagnostics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Mar 30, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 33004838, 25741868
SCV004686395	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 1, 2024)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 33004838, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002502246

AiLife Diagnostics, AiLife Diagnostics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Mar 30, 2022)

germline

clinical testing

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

SCV004686395

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 1, 2024)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	2	not provided	not provided	not provided	not provided	clinical testing
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

Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders.

Wang T, Hoekzema K, Vecchio D, Wu H, Sulovari A, Coe BP, Gillentine MA, Wilfert AB, Perez-Jurado LA, Kvarnung M, Sleyp Y, Earl RK, Rosenfeld JA, Geisheker MR, Han L, Du B, Barnett C, Thompson E, Shaw M, Carroll R, Friend K, Catford R, et al.

Nat Commun. 2020 Oct 1;11(1):4932. doi: 10.1038/s41467-020-18723-y. Erratum in: Nat Commun. 2020 Oct 21;11(1):5398. doi: 10.1038/s41467-020-19289-5.

PubMed [citation]

PMID:: 33004838
PMCID:: PMC7530681

See all PubMed Citations (3)

Details of each submission

From AiLife Diagnostics, AiLife Diagnostics, SCV002502246.1

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

#	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		2	not provided	not provided	not provided

From Invitae, SCV004686395.1

#	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 glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1225 of the MYH9 protein (p.Glu1225Lys). This variant is present in population databases (rs770864107, gnomAD 0.004%). This missense change has been observed in individual(s) with MYH9-related disorders (PMID: 33004838). ClinVar contains an entry for this variant (Variation ID: 1678043). 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 not expected to disrupt MYH9 protein function with a negative predictive value of 80%. 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

Last Updated: Mar 5, 2024

ClinVar

Relating variation to medicine