NM_033380.3(COL4A5):c.1A>G (p.Met1Val) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 4, 2020
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:: RCV001381883.5

Allele description [Variation Report for NM_033380.3(COL4A5):c.1A>G (p.Met1Val)]

NM_033380.3(COL4A5):c.1A>G (p.Met1Val)

Gene:

COL4A5:collagen type IV alpha 5 chain [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xq22.3

Genomic location:

Preferred name:

NM_033380.3(COL4A5):c.1A>G (p.Met1Val)

HGVS:

NC_000023.11:g.108440126A>G
NG_011977.2:g.5203A>G
NG_012059.2:g.4349T>C
NM_000495.5:c.1A>G
NM_033380.3:c.1A>GMANE SELECT
NP_000486.1:p.Met1Val
NP_203699.1:p.Met1Val
LRG_232t1:c.1A>G
LRG_232t2:c.1A>G
LRG_232:g.5203A>G
LRG_232p1:p.Met1Val
LRG_232p2:p.Met1Val
LRG_233:g.4349T>C
NC_000023.10:g.107683356A>G
NG_011977.1:g.5203A>G
NM_000495.4:c.1A>G

Protein change:

M1V

Links:

dbSNP: rs104886050

NCBI 1000 Genomes Browser:

rs104886050

Molecular consequence:

NM_000495.5:c.1A>G - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_033380.3:c.1A>G - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_000495.5:c.1A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_033380.3:c.1A>G - 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
SCV001580457	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 4, 2020)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 24033287, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001580457

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 4, 2020)

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Unbiased next generation sequencing analysis confirms the existence of autosomal dominant Alport syndrome in a relevant fraction of cases.

Fallerini C, Dosa L, Tita R, Del Prete D, Feriozzi S, Gai G, Clementi M, La Manna A, Miglietti N, Mancini R, Mandrile G, Ghiggeri GM, Piaggio G, Brancati F, Diano L, Frate E, Pinciaroli AR, Giani M, Castorina P, Bresin E, Giachino D, De Marchi M, et al.

Clin Genet. 2014 Sep;86(3):252-7. doi: 10.1111/cge.12258. Epub 2013 Oct 17.

PubMed [citation]

PMID:: 24033287

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, SCV001580457.5

#	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 affects the initiator methionine of the COL4A5 mRNA. The next in-frame methionine is located at codon 109. This variant is not present in population databases (ExAC no frequency). Disruption of this initiator codon has been observed in individual(s) with Alport syndrome (PMID: 24033287, Invitae). ClinVar contains an entry for this variant (Variation ID: 24214). This variant disrupts the p.Gly105 amino acid residue in COL4A5. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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: Sep 29, 2024

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