VCV000542361.14 - ClinVar

NM_005219.5(DIAPH1):c.1821TCC[14] (p.Pro618_Pro620dup)

Germline

Classification

criteria provided, conflicting classifications. Learn more about how ClinVar calculates review status.

Conflicting classifications of pathogenicity
Uncertain significance(2); Likely benign(2)

4 out of 5 submissions contributed to this classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_005219.5(DIAPH1):c.1821TCC[14] (p.Pro618_Pro620dup)

Variation ID: 542361 Accession: VCV000542361.14

Type and length

Microsatellite, 9 bp

Location

Cytogenetic: 5q31.3 5: 141573996-141573997 (GRCh38) [ NCBI UCSC ] 5: 140953563-140953564 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Oct 10, 2018	Feb 23, 2026	Jun 10, 2025

HGVS

Nucleotide	Protein	Molecular consequence
NM_005219.5:c.1821TCC[14] MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_005210.3:p.Pro618_Pro620dup	inframe insertion
NM_005219.5:c.1845_1853dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NM_001079812.3:c.1794TCC[14]	NP_001073280.1:p.Pro609_Pro611dup	inframe insertion
NM_001314007.2:c.1821TCC[14]	NP_001300936.1:p.Pro618_Pro620dup	inframe insertion
NM_005219.4:c.1845_1853dup9
NC_000005.10:g.141573998GAG[14]
NC_000005.9:g.140953565GAG[14]
NG_011594.2:g.50027TCC[14]
LRG_1117:g.50027TCC[14]
LRG_1117t1:c.1794TCC[14]	LRG_1117p1:p.Pro609_Pro611dup
LRG_1117t2:c.1821TCC[14]	LRG_1117p2:p.Pro618_Pro620dup

... more HGVS ... less HGVS

Protein change

Other names

p.Pro618_Pro620dup

Canonical SPDI

NC_000005.10:141573996:GGAGGAGGAGGAGGAGGAGGAGGAGGAGGAGGAG:GGAGGAGGAGGAGGAGGAGGAGGAGGAGGAGGAGGAGGAGGAG

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

ClinGen: CA563502799 dbSNP: rs3075570 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
DIAPH1		-	-	GRCh38 GRCh37	1894	1912

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Autosomal dominant nonsyndromic hearing loss 1 Progressive microcephaly-seizures-cortical blindness-developmental delay syndrome	Uncertain significance (1)	criteria provided, single submitter	Nov 12, 2020	RCV000652770.11
DIAPH1-related disorder	Likely benign (1)	no assertion criteria provided	Jun 26, 2019	RCV003918079.2
Inborn genetic diseases	Likely benign (1)	criteria provided, single submitter	Oct 26, 2023	RCV004025885.1
not provided	Conflicting classifications of pathogenicity (2)	criteria provided, conflicting classifications	Jun 10, 2025	RCV004692047.2

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	Expand all rows Collapse all rows Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Uncertain significance (Nov 12, 2020) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Progressive microcephaly-seizures-cortical blindness-developmental delay syndrome Autosomal dominant nonsyndromic hearing loss 1 Explanation for multiple conditions: Uncertain. The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases.	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000774641.9 First in ClinVar: May 28, 2018 Last updated: Feb 23, 2026	Publications: PubMed (1) PubMed: 28492532 Comment: show 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. Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the duplicated amino acids is currently unknown. This variant has not been reported in the literature in individuals with DIAPH1-related disease. ClinVar contains an entry for this variant (Variation ID: 542361). This variant is not present in population databases (ExAC no frequency). This variant, c.1845_1853dupTCCTCCTCC, results in the insertion of 3 amino acids to the DIAPH1 protein (p.Pro618_Pro620dup), but otherwise preserves the integrity of the reading frame. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Likely benign (Oct 26, 2023) C Contributing to aggregate classification	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Inborn genetic diseases	Ambry Genetics Accession: SCV004857586.1 First in ClinVar: May 01, 2024 Last updated: May 01, 2024	Comment: show This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Uncertain significance (-) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	not provided (Autosomal recessive inheritance)	Breakthrough Genomics, Breakthrough Genomics Accession: SCV005188643.1 First in ClinVar: Aug 18, 2024 Last updated: Aug 18, 2024	Observation: 1 Collection method: not provided Allele origin: germline Affected status: yes Observation 1 Collection method: not provided Allele origin: germline Affected status: yes

Likely benign (Jun 10, 2025) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	not provided	Mayo Clinic Laboratories, Mayo Clinic Accession: SCV007324304.1 First in ClinVar: Jan 17, 2026 Last updated: Jan 17, 2026	Comment: show BS1, BP3 (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Number of individuals with the variant: 2

Likely benign (Jun 26, 2019) N Not contributing to aggregate classification	no assertion criteria provided	DIAPH1-related condition	PreventionGenetics, part of Exact Sciences Accession: SCV004732173.2 First in ClinVar: Mar 16, 2024 Last updated: Oct 08, 2024	Comment: show This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Comment:

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. Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the duplicated amino acids is currently unknown. This variant has not been reported in the literature in individuals with DIAPH1-related disease. ClinVar contains an entry for this variant (Variation ID: 542361). This variant is not present in population databases (ExAC no frequency). This variant, c.1845_1853dupTCCTCCTCC, results in the insertion of 3 amino acids to the DIAPH1 protein (p.Pro618_Pro620dup), but otherwise preserves the integrity of the reading frame.

Comment:

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

Citations for germline classification of this variant

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for rs3075570 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Feb 24, 2026