NM_000255.4(MMUT):c.257C>T (p.Pro86Leu) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 20, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV001376596.5

Allele description [Variation Report for NM_000255.4(MMUT):c.257C>T (p.Pro86Leu)]

NM_000255.4(MMUT):c.257C>T (p.Pro86Leu)

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.257C>T (p.Pro86Leu)

HGVS:

NC_000006.12:g.49459210G>A
NG_007100.1:g.8930C>T
NM_000255.4:c.257C>TMANE SELECT
NP_000246.2:p.Pro86Leu
NC_000006.11:g.49426923G>A
NM_000255.3:c.257C>T

Protein change:

P86L

Links:

dbSNP: rs769348060

NCBI 1000 Genomes Browser:

rs769348060

Molecular consequence:

NM_000255.4:c.257C>T - 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
SCV001237344	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 20, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 16281286, 24330302, 27233228, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001237344

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 20, 2023)

germline

clinical testing

PubMed (4)
[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	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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

Asymptomatic methylmalonic acidemia in a homozygous MUT mutation (p.P86L).

Underhill HR, Hahn SH, Hale SL, Merritt JL 2nd.

Pediatr Int. 2013 Dec;55(6):e156-8. doi: 10.1111/ped.12195.

PubMed [citation]

PMID:: 24330302

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001237344.5

#	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 proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 86 of the MUT protein (p.Pro86Leu). This variant is present in population databases (rs769348060, gnomAD 0.01%). This missense change has been observed in individual(s) with methylmalonic acidemia due to methylmalonyl-CoA mutase deficiency (PMID: 16281286, 24330302, 27233228). ClinVar contains an entry for this variant (Variation ID: 553773). 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 MUT protein function with a positive predictive value of 95%. 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

Last Updated: Oct 8, 2024

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