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NM_015443.4(KANSL1):c.2260G>A (p.Val754Met) AND Koolen-de Vries syndrome

Clinical significance:Uncertain significance (Last evaluated: Aug 22, 2022)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:

Allele description [Variation Report for NM_015443.4(KANSL1):c.2260G>A (p.Val754Met)]

NM_015443.4(KANSL1):c.2260G>A (p.Val754Met)

KANSL1:KAT8 regulatory NSL complex subunit 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_015443.4(KANSL1):c.2260G>A (p.Val754Met)
  • NC_000017.11:g.46039159C>T
  • NG_032784.1:g.191216G>A
  • NM_001193465.2:c.2260G>A
  • NM_001193466.2:c.2260G>A
  • NM_001379198.1:c.2260G>A
  • NM_015443.4:c.2260G>AMANE SELECT
  • NP_001180394.1:p.Val754Met
  • NP_001180395.1:p.Val754Met
  • NP_001366127.1:p.Val754Met
  • NP_056258.1:p.Val754Met
  • NC_000017.10:g.44116525C>T
Protein change:
dbSNP: rs773184800
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_001193465.2:c.2260G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001193466.2:c.2260G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001379198.1:c.2260G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_015443.4:c.2260G>A - missense variant - [Sequence Ontology: SO:0001583]


Koolen-de Vries syndrome (KDVS)
KANSL1-Related Intellectual Disability Syndrome
MONDO: MONDO:0012496; MedGen: C1864871; Orphanet: 96169; OMIM: 610443

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV001532720Invitaecriteria provided, single submitter
Uncertain significance
(Aug 22, 2022)
germlineclinical testing

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

Summary from all submissions

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



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):240-242.

PubMed [citation]

Details of each submission

From Invitae, SCV001532720.3

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


This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 754 of the KANSL1 protein (p.Val754Met). This variant is present in population databases (rs773184800, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with KANSL1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1036055). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The methionine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.

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

Last Updated: Feb 7, 2023