NM_020806.5(GPHN):c.2195G>A (p.Arg732His) AND Sulfite oxidase deficiency due to molybdenum cofactor deficiency type C

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 28, 2025
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:: RCV002602412.5

Allele description [Variation Report for NM_020806.5(GPHN):c.2195G>A (p.Arg732His)]

NM_020806.5(GPHN):c.2195G>A (p.Arg732His)

Gene:

GPHN:gephyrin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

14q23.3

Genomic location:

Preferred name:

NM_020806.5(GPHN):c.2195G>A (p.Arg732His)

HGVS:

NC_000014.9:g.67180822G>A
NG_008875.2:g.677677G>A
NM_001024218.2:c.2096G>A
NM_001377514.1:c.2255G>A
NM_001377515.1:c.2225G>A
NM_001377516.1:c.2216G>A
NM_001377517.1:c.2168G>A
NM_001377518.1:c.2153G>A
NM_001377519.1:c.2135G>A
NM_020806.4:c.2195G>A
NM_020806.5:c.2195G>AMANE SELECT
NP_001019389.1:p.Arg699His
NP_001364443.1:p.Arg752His
NP_001364444.1:p.Arg742His
NP_001364445.1:p.Arg739His
NP_001364446.1:p.Arg723His
NP_001364447.1:p.Arg718His
NP_001364448.1:p.Arg712His
NP_065857.1:p.Arg732His
NC_000014.8:g.67647539G>A
NG_008875.1:g.678415G>A

Protein change:

R699H

Links:

dbSNP: rs756728918

Molecular consequence:

NM_001024218.2:c.2096G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001377514.1:c.2255G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001377515.1:c.2225G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001377516.1:c.2216G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001377517.1:c.2168G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001377518.1:c.2153G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001377519.1:c.2135G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_020806.5:c.2195G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Sulfite oxidase deficiency due to molybdenum cofactor deficiency type C
Synonyms:: Molybdenum cofactor deficiency, complementation group C; Molybdenum cofactor deficiency C
Identifiers:: MONDO: MONDO:0014212; MedGen: C1854990; Orphanet: 833; OMIM: 615501

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003492070	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 28, 2025)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003492070

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 28, 2025)

germline

clinical testing

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	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, SCV003492070.4

#	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 arginine, which is basic and polar, with histidine, which is basic and polar, at codon 732 of the GPHN protein (p.Arg732His). This variant is present in population databases (rs756728918, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with GPHN-related conditions. ClinVar contains an entry for this variant (Variation ID: 2175728). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt GPHN protein function with a positive predictive value of 80%. 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

Last Updated: Feb 15, 2026

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