NM_019032.6(ADAMTSL4):c.232C>T (p.Leu78Phe) AND not provided

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (3 submissions)
Last evaluated:: Oct 14, 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:: RCV001859744.6

Allele description

NM_019032.6(ADAMTSL4):c.232C>T (p.Leu78Phe)

Genes:

ADAMTSL4:ADAMTS like 4 [Gene - OMIM - HGNC]
ADAMTSL4-AS2:ADAMTSL4 antisense RNA 2 [Gene - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q21.2

Genomic location:

Preferred name:

NM_019032.6(ADAMTSL4):c.232C>T (p.Leu78Phe)

HGVS:

NC_000001.11:g.150553051C>T
NG_012172.1:g.8630C>T
NM_001288607.2:c.232C>T
NM_001288608.2:c.232C>T
NM_001378596.1:c.232C>T
NM_019032.5:c.232C>T
NM_019032.6:c.232C>TMANE SELECT
NM_025008.5:c.232C>T
NP_001275536.1:p.Leu78Phe
NP_001275537.1:p.Leu78Phe
NP_001365525.1:p.Leu78Phe
NP_061905.2:p.Leu78Phe
NP_079284.2:p.Leu78Phe
NC_000001.10:g.150525527C>T
NM_019032.4:c.232C>T
NM_019032.6:c.232C>T

Protein change:

L78F

Links:

dbSNP: rs147688134

NCBI 1000 Genomes Browser:

rs147688134

Molecular consequence:

NM_001288607.2:c.232C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001288608.2:c.232C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001378596.1:c.232C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_019032.6:c.232C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_025008.5:c.232C>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
SCV002251987	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 14, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003824979	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Oct 31, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV005186889	Breakthrough Genomics, Breakthrough Genomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance	germline	not provided	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002251987

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 14, 2022)

germline

clinical testing

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

SCV003824979

Revvity Omics, Revvity

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Oct 31, 2020)

germline

clinical testing

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

SCV005186889

Breakthrough Genomics, Breakthrough Genomics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance

germline

not provided

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	not provided	not provided	not provided
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

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

Details of each submission

From Invitae, SCV002251987.2

#	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, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 78 of the ADAMTSL4 protein (p.Leu78Phe). This variant is present in population databases (rs147688134, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with ADAMTSL4-related conditions. ClinVar contains an entry for this variant (Variation ID: 292518). 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 ADAMTSL4 protein function. 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 Revvity Omics, Revvity, SCV003824979.2

#	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

From Breakthrough Genomics, Breakthrough Genomics, SCV005186889.1

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

#	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		not provided	not provided	not provided	not provided

Last Updated: Aug 18, 2024

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