NM_001352514.2(HLCS):c.2371C>G (p.Leu791Val) AND Holocarboxylase synthetase deficiency

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Aug 30, 2021
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:: RCV001323872.8

Allele description [Variation Report for NM_001352514.2(HLCS):c.2371C>G (p.Leu791Val)]

NM_001352514.2(HLCS):c.2371C>G (p.Leu791Val)

Gene:

HLCS:holocarboxylase synthetase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

21q22.13

Genomic location:

Preferred name:

NM_001352514.2(HLCS):c.2371C>G (p.Leu791Val)

HGVS:

NC_000021.9:g.36756621G>C
NG_016193.2:g.238774C>G
NM_000411.8:c.1930C>G
NM_001242784.3:c.1930C>G
NM_001242785.2:c.1930C>G
NM_001352514.2:c.2371C>GMANE SELECT
NM_001352515.2:c.1930C>G
NM_001352516.2:c.1930C>G
NM_001352517.1:c.1930C>G
NM_001352518.2:c.1930C>G
NP_000402.3:p.Leu644Val
NP_001229713.1:p.Leu644Val
NP_001229714.1:p.Leu644Val
NP_001339443.1:p.Leu791Val
NP_001339444.1:p.Leu644Val
NP_001339445.1:p.Leu644Val
NP_001339446.1:p.Leu644Val
NP_001339447.1:p.Leu644Val
NC_000021.8:g.38128922G>C
NR_148020.2:n.2455C>G
NR_148021.1:n.2612C>G

Protein change:

L644V

Links:

dbSNP: rs748447457

NCBI 1000 Genomes Browser:

rs748447457

Molecular consequence:

NM_000411.8:c.1930C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001242784.3:c.1930C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001242785.2:c.1930C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001352514.2:c.2371C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001352515.2:c.1930C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001352516.2:c.1930C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001352517.1:c.1930C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001352518.2:c.1930C>G - missense variant - [Sequence Ontology: SO:0001583]
NR_148020.2:n.2455C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_148021.1:n.2612C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Holocarboxylase synthetase deficiency
Synonyms:: MULTIPLE CARBOXYLASE DEFICIENCY, EARLY ONSET
Identifiers:: MONDO: MONDO:0009666; MedGen: C0268581; Orphanet: 79242; OMIM: 253270

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
SCV001514807	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 30, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002083718	Natera, Inc.	no assertion criteria provided	Uncertain significance (May 19, 2020)	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001514807

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 30, 2021)

germline

clinical testing

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

SCV002083718

Natera, Inc.

no assertion criteria provided

Uncertain significance
(May 19, 2020)

germline

clinical testing

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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group, Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001514807.3

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

Description

This sequence change replaces leucine with valine at codon 644 of the HLCS protein (p.Leu644Val). The leucine residue is moderately conserved and there is a small physicochemical difference between leucine and valine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with HLCS-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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 Natera, Inc., SCV002083718.1

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

Last Updated: Sep 29, 2024

ClinVar

Relating variation to medicine