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NM_014140.4(SMARCAL1):c.1736C>T (p.Ser579Leu) AND Schimke immuno-osseous dysplasia

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Sep 14, 2021)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:

Allele description [Variation Report for NM_014140.4(SMARCAL1):c.1736C>T (p.Ser579Leu)]

NM_014140.4(SMARCAL1):c.1736C>T (p.Ser579Leu)

SMARCAL1:SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a like 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_014140.4(SMARCAL1):c.1736C>T (p.Ser579Leu)
  • NC_000002.12:g.216447043C>T
  • NG_009771.1:g.39630C>T
  • NM_001127207.2:c.1736C>T
  • NM_014140.4:c.1736C>TMANE SELECT
  • NP_001120679.1:p.Ser579Leu
  • NP_054859.2:p.Ser579Leu
  • LRG_108t1:c.1736C>T
  • LRG_108:g.39630C>T
  • NC_000002.11:g.217311766C>T
  • NM_014140.3:c.1736C>T
Protein change:
dbSNP: rs1694331040
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_001127207.2:c.1736C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_014140.4:c.1736C>T - missense variant - [Sequence Ontology: SO:0001583]


Schimke immuno-osseous dysplasia (SIOD)
Spondyloepiphyseal dysplasia nephrotic syndrome; Schimke syndrome; Schimke immunoosseous dysplasia
MONDO: MONDO:0009458; MedGen: C0877024; Orphanet: 1830; OMIM: 242900

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV001388449Invitaecriteria provided, single submitter
(Sep 14, 2021)
germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

SCV001425266Molecular Biology Laboratory, Fundació Puigvert - KidneyPanel_2020criteria provided, single submitter
Likely pathogenic
(Feb 1, 2020)

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedresearch
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing



Mutant chromatin remodeling protein SMARCAL1 causes Schimke immuno-osseous dysplasia.

Boerkoel CF, Takashima H, John J, Yan J, Stankiewicz P, Rosenbarker L, André JL, Bogdanovic R, Burguet A, Cockfield S, Cordeiro I, Fründ S, Illies F, Joseph M, Kaitila I, Lama G, Loirat C, McLeod DR, Milford DV, Petty EM, Rodrigo F, Saraiva JM, et al.

Nat Genet. 2002 Feb;30(2):215-20. Epub 2002 Jan 22.

PubMed [citation]

Schimke immunoosseous dysplasia: suggestions of genetic diversity.

Clewing JM, Fryssira H, Goodman D, Smithson SF, Sloan EA, Lou S, Huang Y, Choi K, Lücke T, Alpay H, André JL, Asakura Y, Biebuyck-Gouge N, Bogdanovic R, Bonneau D, Cancrini C, Cochat P, Cockfield S, Collard L, Cordeiro I, Cormier-Daire V, Cransberg K, et al.

Hum Mutat. 2007 Mar;28(3):273-83.

PubMed [citation]
See all PubMed Citations (8)

Details of each submission

From Invitae, SCV001388449.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)


This sequence change replaces serine with leucine at codon 579 of the SMARCAL1 protein (p.Ser579Leu). The serine residue is highly conserved and there is a large physicochemical difference between serine and leucine. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individual(s) with Schimke immuno-osseous dysplasia (PMID: 11799392, 17089404, 22998683). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 945899). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Experimental studies have shown that this missense change affects SMARCAL1 function (PMID: 18805831, 26195148). For these reasons, this variant has been classified as Pathogenic.

OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Molecular Biology Laboratory, Fundació Puigvert - KidneyPanel_2020, SCV001425266.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedresearch PubMed (2)
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: May 24, 2022

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