NM_006306.4(SMC1A):c.1904G>A (p.Arg635His) AND Congenital muscular hypertrophy-cerebral syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 11, 2023
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:: RCV003089206.3

Allele description [Variation Report for NM_006306.4(SMC1A):c.1904G>A (p.Arg635His)]

NM_006306.4(SMC1A):c.1904G>A (p.Arg635His)

Gene:

SMC1A:structural maintenance of chromosomes 1A [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xp11.22

Genomic location:

Preferred name:

NM_006306.4(SMC1A):c.1904G>A (p.Arg635His)

HGVS:

NC_000023.11:g.53405500C>T
NG_006988.2:g.22171G>A
NM_001281463.1:c.1838G>A
NM_006306.4:c.1904G>AMANE SELECT
NP_001268392.1:p.Arg613His
NP_006297.2:p.Arg635His
LRG_773t1:c.1838G>A
LRG_773:g.22171G>A
LRG_773p1:p.Arg613His
NC_000023.10:g.53432432C>T
NM_006306.2:c.1904G>A

Protein change:

R613H

Links:

dbSNP: rs2146599709

NCBI 1000 Genomes Browser:

rs2146599709

Molecular consequence:

NM_001281463.1:c.1838G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_006306.4:c.1904G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Congenital muscular hypertrophy-cerebral syndrome (CDLS2)
Synonyms:: Cornelia de Lange syndrome 2
Identifiers:: MONDO: MONDO:0010370; MedGen: C1802395; Orphanet: 199; OMIM: 300590

Recent activity

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Homo sapiens leucine rich repeat transmembrane neuronal 4 (LRRTM4), transcript v...
Homo sapiens leucine rich repeat transmembrane neuronal 4 (LRRTM4), transcript variant 6, non-coding RNA
gi|1890527350|ref|NR_146416.2|

Nucleotide
BJ634128 NIBB Mochii normalized Xenopus early gastrula library Xenopus laevis cD...
BJ634128 NIBB Mochii normalized Xenopus early gastrula library Xenopus laevis cDNA clone XL181j10 3', mRNA sequence
gi|37286995|gnl|dbEST|19939139|dbj| 128.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003445241	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 11, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 28548707, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003445241

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 11, 2023)

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

Phenotypes and genotypes in individuals with SMC1A variants.

Huisman S, Mulder PA, Redeker E, Bader I, Bisgaard AM, Brooks A, Cereda A, Cinca C, Clark D, Cormier-Daire V, Deardorff MA, Diderich K, Elting M, van Essen A, FitzPatrick D, Gervasini C, Gillessen-Kaesbach G, Girisha KM, Hilhorst-Hofstee Y, Hopman S, Horn D, Isrie M, et al.

Am J Med Genet A. 2017 Aug;173(8):2108-2125. doi: 10.1002/ajmg.a.38279. Epub 2017 May 26.

PubMed [citation]

PMID:: 28548707

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, SCV003445241.2

#	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 replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 635 of the SMC1A protein (p.Arg635His). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with SMC1A-related conditions (PMID: 28548707). ClinVar contains an entry for this variant (Variation ID: 1678779). 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 expected to disrupt SMC1A 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: Sep 29, 2024

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