NM_006019.4(TCIRG1):c.1331G>T (p.Arg444Leu) AND Autosomal recessive osteopetrosis 1

Germline classification:: Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:: Jan 5, 2024
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:: RCV000005797.6

Allele description [Variation Report for NM_006019.4(TCIRG1):c.1331G>T (p.Arg444Leu)]

NM_006019.4(TCIRG1):c.1331G>T (p.Arg444Leu)

Gene:

TCIRG1:T cell immune regulator 1, ATPase H+ transporting V0 subunit a3 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11q13.2

Genomic location:

Preferred name:

NM_006019.4(TCIRG1):c.1331G>T (p.Arg444Leu)

HGVS:

NC_000011.10:g.68047672G>T
NG_007878.1:g.13657G>T
NM_001351059.2:c.437G>T
NM_006019.4:c.1331G>TMANE SELECT
NM_006053.4:c.683G>T
NP_001337988.1:p.Arg146Leu
NP_006010.2:p.Arg444Leu
NP_006044.1:p.Arg228Leu
LRG_115:g.13657G>T
NC_000011.9:g.67815139G>T
Q13488:p.Arg444Leu

Protein change:

R146L; ARG444LEU

Links:

UniProtKB: Q13488#VAR_019570; OMIM: 604592.0006; dbSNP: rs137853151

NCBI 1000 Genomes Browser:

rs137853151

Molecular consequence:

NM_001351059.2:c.437G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_006019.4:c.1331G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_006053.4:c.683G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Autosomal recessive osteopetrosis 1
Synonyms:: ALBERS-SCHONBERG DISEASE, AUTOSOMAL RECESSIVE; Osteopetrosis infantile malignant 1; Marble bones autosomal recessive; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009815; MedGen: C1850127; Orphanet: 667; OMIM: 259700

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000025979	OMIM	no assertion criteria provided	Pathogenic (Aug 15, 2001)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV004205773	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Dec 27, 2023)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV005684258	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jan 5, 2024)	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

SCV000025979

OMIM

no assertion criteria provided

Pathogenic
(Aug 15, 2001)

germline

literature only

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

SCV004205773

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Dec 27, 2023)

unknown

clinical testing

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

SCV005684258

Fulgent Genetics, Fulgent Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jan 5, 2024)

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	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

The mutational spectrum of human malignant autosomal recessive osteopetrosis.

Sobacchi C, Frattini A, Orchard P, Porras O, Tezcan I, Andolina M, Babul-Hirji R, Baric I, Canham N, Chitayat D, Dupuis-Girod S, Ellis I, Etzioni A, Fasth A, Fisher A, Gerritsen B, Gulino V, Horwitz E, Klamroth V, Lanino E, Mirolo M, Musio A, et al.

Hum Mol Genet. 2001 Aug 15;10(17):1767-73.

PubMed [citation]

PMID:: 11532986

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 OMIM, SCV000025979.2

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

Description

Among 9 Costa Rican families with autosomal recessive osteopetrosis (OPTB1; 259700), Sobacchi et al. (2001) found an arg444-to-leu (R444L) missense mutation among the mutant alleles in 5 of 9 families. One of 5 families was homozygous for the mutation, which alters a highly conserved residue that may lie within a membrane-spanning region of the protein.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Baylor Genetics, SCV004205773.2

#	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	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Fulgent Genetics, Fulgent Genetics, SCV005684258.1

#	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

Last Updated: Apr 7, 2025

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