NM_000255.4(MMUT):c.1718T>C (p.Phe573Ser) AND not provided

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Nov 25, 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:: RCV000725410.6

Allele description [Variation Report for NM_000255.4(MMUT):c.1718T>C (p.Phe573Ser)]

NM_000255.4(MMUT):c.1718T>C (p.Phe573Ser)

Gene:

MMUT:methylmalonyl-CoA mutase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6p12.3

Genomic location:

Preferred name:

NM_000255.4(MMUT):c.1718T>C (p.Phe573Ser)

HGVS:

NC_000006.12:g.49441930A>G
NG_007100.1:g.26210T>C
NM_000255.4:c.1718T>CMANE SELECT
NP_000246.2:p.Phe573Ser
NC_000006.11:g.49409643A>G
NM_000255.3:c.1718T>C
P22033:p.Phe573Ser

Protein change:

F573S

Links:

UniProtKB: P22033#VAR_026625; dbSNP: rs775593146

NCBI 1000 Genomes Browser:

rs775593146

Molecular consequence:

NM_000255.4:c.1718T>C - missense variant - [Sequence Ontology: SO:0001583]

Observations:

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
SCV000336766	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Likely pathogenic (Nov 25, 2015)	germline	clinical testing	Citation Link,
SCV003299598	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 25, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 25125334, 16281286, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000336766

Eurofins Ntd Llc (ga)

criteria provided, single submitter

(EGL Classification Definitions 2015)

Likely pathogenic
(Nov 25, 2015)

germline

clinical testing

Citation Link,

SCV003299598

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 25, 2022)

germline

clinical testing

PubMed (3)
[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	unknown	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Functional characterization and categorization of missense mutations that cause methylmalonyl-CoA mutase (MUT) deficiency.

Forny P, Froese DS, Suormala T, Yue WW, Baumgartner MR.

Hum Mutat. 2014 Dec;35(12):1449-58. doi: 10.1002/humu.22633.

PubMed [citation]

PMID:: 25125334
PMCID:: PMC4441004

Spectrum of mutations in mut methylmalonic acidemia and identification of a common Hispanic mutation and haplotype.

Worgan LC, Niles K, Tirone JC, Hofmann A, Verner A, Sammak A, Kucic T, Lepage P, Rosenblatt DS.

Hum Mutat. 2006 Jan;27(1):31-43.

PubMed [citation]

PMID:: 16281286

See all PubMed Citations (3)

Details of each submission

From Eurofins Ntd Llc (ga), SCV000336766.4

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

#	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		1	not provided	not provided	not provided

From Invitae, SCV003299598.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This variant is present in population databases (rs775593146, gnomAD 0.007%). For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects MUT function (PMID: 25125334). 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 MUT protein function. ClinVar contains an entry for this variant (Variation ID: 284235). This missense change has been observed in individual(s) with methylmalonic aciduria (PMID: 16281286). This sequence change replaces phenylalanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 573 of the MUT protein (p.Phe573Ser).

#	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: Feb 20, 2024

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